The treatment of lung cancer should be “based on the patient’s physical and mental condition, the specific location, pathological type, invasion range (stage) and development trend of the tumor, combined with changes in cellular molecular biology, the existing multidisciplinary effective treatment means should be applied in a planned and rational manner to achieve the best therapeutic effect at the most appropriate economic cost, while maximizing the patient’s quality of life. .”
Section I. Surgical treatment of lung cancer
(I) Most suitable lung cancer for surgical treatment
The most suitable lung cancers for surgical treatment are stage I and II non-small cell lung cancers and some selected stage III A such as T3N1M0 lung cancers (Table 4). Patients with N2 who have clear mediastinal lymph node metastases on imaging should not undergo immediate surgical resection. As for stage IIIB and IV lung cancer, surgery should not be listed as the primary treatment.
(B) According to the degree of completeness and nature of surgery, surgery for lung cancer can be divided into four types: complete resection, incomplete resection, indeterminate resection and dissection of the chest
Complete resection: In 2005, the Staging Committee of the International Association for the Study of Lung Cancer defined complete resection of lung cancer as: (1) all margins including bronchi, arteries, veins, peribronchial tissues and tissues near the tumor; (2) systemic or lobar systemic lymph node dissection, which must include six groups of lymph nodes, three of which are from the intrapulmonary (lobar, interlobular or segmental) and lung Only if all four conditions are met can the lung be classified as a complete resection. This definition, in addition to meeting the conditions originally specified for surgery in which the primary lung cancer and the hilar mediastinal lymph nodes are completely resected without visual or microscopic cancer residue, also queues up the suspicious (incompletely resection) also with 4 requirements. (1) residual tumor at the cut edge; (2) extra nodal invasion of mediastinal lymph nodes or marginal lymph nodes of resected lobe; (3) positive lymph nodes but not resectable (R2); (4) positive cancer cells in pleural or pericardial cavity fluid. The staging committee also specifically listed a category of procedures called “uncertain resec-tion” – all margins are negative microscopically but one of the following four conditions is present: (1) lymph node clearance does not meet the (2) the highest mediastinal lymph nodes are positive but resected; (3) the bronchial margins are carcinoma in situ; (4) the pleural cavity washings are cytologically positive. As can be seen, indeterminate resection refers to the situation where there is no evidence of residual tumor but the operation does not meet the criteria of complete resection, and exploratory thoracotomy (explore thoractomy or open and close operation) refers to the operation where only the thorax is cut but the cancer is not removed or the operation where only biopsy is performed.
The code for complete resection is R0, for microscopic cancer residual operation is R1, and for sarcoid cancer residual operation is R2.
(C) Pre-operative evaluation of lung cancer patients
1.The preoperative evaluation of lung cancer patients should comprehensively evaluate their systemic status, including physical condition, nutritional status, previous medical history and the presence of other concomitant systemic diseases, etc.
2. Perioperative complications increase with the age of the patient, and advanced age is not a contraindication to surgery when there are no other concomitant diseases. stage I and II lung cancer patients over 70 years old and stage I lung cancer patients over 80 years old can safely undergo lobectomy or wedge resection, but total lung resection should be done with great caution.
3. Preoperative lung function evaluation should be performed for all lung cancer patients, and a forced expiratory volume in one second (FEV1) greater than 1.5 L can safely undergo lobectomy, and greater than 2 L can safely undergo total lobectomy (adjuvant chemotherapy can be considered for stage IB with surgical mortality of 4 cm)
For completely resected stage I lung cancer, especially for stage IA patients with T1N0M0, the best current evidence is that no adjuvant therapy, especially adjuvant radiotherapy, is required. 1995 meta-analysis showed that adjuvant chemotherapy with platinum-containing regimens may have a tendency to improve long-term survival, but it was not statistically significant. the CALGB 9633 study suggested that postoperative stage I B NSCLC adjuvant chemotherapy with teso carboplatin failed to improve 5-year survival, but improved progression-free survival. Subgroup analysis showed that adjuvant chemotherapy improved 5-year survival in those with tumor diameter >4 cm.
4.Stage I lung cancer with complete resection, especially T1N0M0 lung cancer, can be considered for rigorous adjuvant biotherapy clinical randomized controlled study
Japanese scholars reported a clinical randomized controlled study in which 400 patients with stage I squamous carcinoma were randomly divided into two groups of oral biomodulator Bestatin or placebo after surgery, and the 5-year survival rate was 81.0% in Bestatin Shao and 74.2% in placebo group (P = 0.02), and the 5-year tumor-free survival rate was 71.6% versus 62.0%. Most of the current domestic and international studies on adjuvant biologic therapy for early-stage NSCLC are evidence of low credibility, so it is recommended that randomized controlled clinical studies in this area be carried out in hospitals with conditions.
5. Incompletely resected stage I lung cancer with positive cut margins, reoperation is recommended
For incompletely resected stage I lung cancer with positive margins (R1), reoperation is recommended to convert incomplete resection to complete resection. If surgery is not possible or desired, postoperative radiotherapy + chemotherapy can help to improve survival rate. The 5-year survival rate of postoperative radiotherapy is 30% for microscopically positive incompletely resected stage I lung cancer, and there is no 5-year survival rate for sarcoid positive.
(II) Treatment of stage II lung pain (T1-2N1M0, T3N0M0)
1. Treatment of N1 stage II lung cancer
(1) The preferred treatment for N1 stage II lung cancer is lobectomy plus hilar mediastinal lymph node dissection.
Stage II lung cancer includes two groups: T1N1M0 stage IIA and T2N1M0 and T3N0M0 stage IIB. Like stage I lung cancer, the treatment for stage II lung cancer is mainly surgical resection, such as lobectomy, bilobectomy or total pneumonectomy with hilar mediastinal lymph node dissection. Smaller resections are only considered for those with poor lung function that cannot tolerate lobectomy. In general, lobectomy with hilar mediastinal lymph node dissection is sufficient to completely remove the primary tumor and the involved lymph nodes, and sleeve lobectomy expands the indications for the procedure. In summary, the 5-year postoperative survival rate of 3011 lung cancer surgery cases with pathological stage II(N force) accumulated in 11 hospitals on the literature was 41%, including 52% for T1N1M0, 39% for T2N1M0, 47% for squamous carcinoma, and 29% for adenocarcinoma.
(2) Adjuvant chemotherapy is recommended for N1 stage II lung cancer with complete resection. Adjuvant radiotherapy is not required except in clinical trials.
The incidence of recurrent metastases after Nl stage II lung cancer is about 54%, of which ?4% are distant metastases and 26% are local recurrences.
The results of current evidence-based medical studies show that postoperative radiotherapy is not beneficial but harmful to long-term survival; recent large-scale studies such as IALT, BRl0, and ANITA have shown that postoperative adjuvant chemotherapy with platinum-containing regimens can prolong survival. A prospective randomized controlled study in France suggested that preoperative chemotherapy with MVP regimens may be beneficial for survival in this stage of lung cancer, but this has not been confirmed by additional studies. Therefore, neoadjuvant chemotherapy, immunotherapy, and adjuvant radiotherapy for patients in this stage are still in the research stage.
2.Treatment of T3 stage II lung cancer
(1) Surgical resection is still the main treatment for T3 stage II lung cancer.
Stage T3Ⅱ lung cancer is characterized by the presence of lymph node metastasis and invasion of the primary tumor, but it is possible to resect it without reconstruction. Stage T3 II lung cancer can be further classified into 4 types according to the extent of invasion: invasion of chest wall, invasion of mediastinum, invasion of main bronchus less than 2 cm from the bulge, and Pancoast tumor. This type of lung cancer is still mainly resected by surgery.
(2) For stage T3 II lung cancer that invades the chest wall or mediastinum or is close to the trachea, if the case is evaluated preoperatively as resectable, the preferred treatment is lobectomy or total pneumonectomy including invaded soft tissue and mediastinal lymph node dissection.
When the tumor invades the mural pleura or chest wall, whole chest wall resection should be performed. If the tumor invades the wall pleura or chest wall, the whole chest wall should be resected, and the resection area should be at least 2 cm from the upper and lower edge of the nearest rib, and the length of the invaded rib should be at least 5 cm from the tumor. If there is no tumor tissue on the free surface, extra pleural resection can be performed. If there is any resistance in the free surface, the free surface should be stopped and the whole chest wall should be resected instead.
For T3N0M0 lung cancer invading the chest wall, the 5-year survival rate is 50%-60% after complete resection, and the 5-year survival rate is 27% for T3N0M0 lung cancer invading the mediastinum.
(3) Completely resected invasive stage II lung cancer of the chest wall is recommended for adjuvant chemotherapy, and adjuvant radiotherapy is not required except in clinical trials.
(4) Surgery with positive margins is incomplete resection, and if re-operation can resect cleanly, re-operation should be considered to change the surgery from incomplete resection to complete resection, otherwise radiation therapy combined with chemotherapy should be given.
(5) For cases treated with chemoradiotherapy first, the possibility of surgical resection should be evaluated at any time during treatment.
If the preoperative evaluation is unresectable, the preferred treatment is concurrent radiotherapy. After 2-3 cycles of chemotherapy and 40Gy radiotherapy, the surgical resectability should be re-evaluated, and surgical resection should be performed if the case is resectable, and radiotherapy should be continued if it is unresectable.
(6) For supraglottic sulcus tumors, if the preoperative evaluation is resectable, the preferred treatment is surgical resection after concurrent chemoradiotherapy.
If the preoperative evaluation is unresectable, the preferred treatment is concurrent radiotherapy, followed by 2-3 cycles of chemotherapy and 40 Gy of radiotherapy, followed by surgical resection if resectable, and continued radiotherapy if unresectable.
The operative mortality rate for supraglottic sulcus tumors ranges from 2.6% to 4%. The overall 5-year postoperative survival rate is 35% (28% to 40%). In case of complete resection, more than 50% can be cured.
(C) Treatment of stage III lung cancer
Stage III lung cancer, also known as locally advanced non-small cell lung cancer, refers to lung cancer with mediastinal lymph node metastasis (N2) or invasion of important mediastinal structures (T4) or supraclavicular lymph node metastasis (N3). According to the 97th International Staging of Lung Cancer, locally advanced non-small cell lung cancer is lung cancer of IIIA or IIIB. The current treatment outcome of this part of NSCLC is not satisfactory, with a 5-year survival rate of 15% to 23% for stage IIIA and only 6% to 7% for stage IIIB.
From the viewpoint of therapeutics, locally advanced NSCLC can be divided into two categories: resectable and unresectable. Resectable locally advanced NSCLC includes some cases with preoperative clinical stage I or II but postoperative pathology reveals mediastinal lymph node metastasis, which is called incidental IIIA NSCLC; it also includes cases with single or multi-station mediastinal lymph node metastasis on imaging but estimated to be completely resectable, and includes some cases with a small amount of malignant pleural fluid, such as D4 cases. Unresectable locally advanced non-small cell lung cancer includes cases with a mediastinal mass on imaging and positive mediastinoscopy, which is called borderline stage IIIA (marginal IIIA) non-small cell lung cancer; it also includes most of D4 and all of N3 non-small cell lung cancer.
1. For resectable N2 locally advanced NSCLC, the currently recommended treatment modality is neoadjuvant chemotherapy with ten surgical resections or surgical excision with bullous adjuvant chemotherapy, and the standard procedure is lobectomy with systematic mediastinal lymph node dissection
Locally advanced NSCLC in clinical N2 has a natural median survival of 7 months. Retrospective studies of large numbers of cases suggest that surgical treatment of these selected N2 cases results in complete resection rates of up to 60%, with 5-year survival rates of approximately 20% to 25% for patients whose postoperative pathology remains N2.
The current randomized controlled clinical studies show that the pattern of preoperative neoadjuvant chemotherapy favors long-term survival in N2 patients, with five RCT studies showing a 5-year survival rate of 28% with preoperative chemotherapy and 16% with surgery alone, with statistically significant differences between preoperative chemotherapy and surgery alone in two of these studies. a 2006 Burddet meta-analysis of 12 clinical studies showed that preoperative chemotherapy increased the 5-year survival rate from 14% to 20%.
The choice of surgical approach for N2 locally advanced non-small cell lung cancer is highly debated in retrospective studies between the advantages and disadvantages of both lobectomy and total pneumonectomy. 1998 Meta-analysis showed that both lobectomy and total pneumonectomy had no effect on survival in N2 patients, but retrospective studies of large numbers of cases suggest that the incidence of mortality is much higher with total pneumonectomy (9%) than with lobectomy (3%). resection (3%), and major complications such as pneumonia, respiratory failure, and heart failure are also seen more often with total pneumonectomy.
The mode of resection of mediastinal lymph nodes has also been debated. However, there are three clinically randomized controlled studies and one well-designed non-randomized study suggesting that systematic mediastinal lymph node dissection is beneficial for accurate staging and improved survival.
(1) A clinical randomized controlled study of preoperative chemotherapy for resectable locally advanced NSCLC is recommended for hospitals that are in a position to do so. Although randomized studies of preoperative chemotherapy have shown its relative survival advantage over surgery alone, there are still few relevant RCT studies and the number of cases per RCT is small, the credibility of the evidence is still insufficient, and the optimal regimen and number of cycles of preoperative chemotherapy are yet to be further investigated. Therefore, it is recommended that randomized controlled clinical studies of preoperative chemotherapy for resectable locally advanced NSCLC be conducted in hospitals with the conditions.
(2) Postoperative adjuvant chemotherapy with 3rd generation platinum-containing regimens is recommended for locally advanced NSCLC after complete resection. Eight randomized controlled clinical studies with 50 or more cases showed 2- and 5-year survival rates of 55% and 37% in the postoperative platinum-containing chemotherapy group and 46% and 32% in the surgery alone group, but only three of these randomized controlled studies showed statistically significant differences.
Successive IALT and ANITA studies published after 2002 showed that adjuvant chemotherapy with NP regimens prolonged survival. However, patients with total pneumonectomy, especially right total pneumonectomy or slow postoperative recovery, PS ≥ 2 or inappropriate for platinum, are not recommended for postoperative adjuvant chemotherapy.
(3) Four cycles of postoperative adjuvant chemotherapy are recommended. The results of studies on the number of cycles of adjuvant chemotherapy after complete resection for locally advanced non-small cell lung cancer are not available. However, the results of three randomized controlled clinical studies on the number of cycles of chemotherapy for advanced non-small cell lung cancer found that 3-4 cycles of chemotherapy were comparable to 6 or more cycles of chemotherapy in terms of survival, but with significantly less toxic side effects.
(4) Locally advanced NSCLC after incomplete resection, postoperative radiotherapy and chemotherapy with platinum-containing regimens are recommended. incomplete resection of NSCLC refers to three conditions in which there is still postoperative residual sarcoid tumor or lymph nodes, or positive microscopic margins, or positive highest mediastinal lymph nodes. The first scenario (R2) has almost no 5-year survival rate, while the second scenario (R1) has a 5-year survival rate of up to 30%. The results of one clinical randomized controlled study showed that postoperative chemoradiotherapy meaningfully reduced the recurrence rate and improved the recurrence-free survival rate.
(5) Resectable locally advanced NSCLC that cannot undergo surgery due to disease or patient preference is treated as unresectable locally advanced NSCLC.
Resectable locally advanced NSCLC that cannot undergo surgery due to disease reasons should be further grouped according to PS status and weight loss index, and for NSCLC with PS2, best supportive care should be the primary means.
3.Treatment of T4N0-1 non-small cell lung cancer
(1) If T4 is defined by satellite nodes, the preferred treatment for this type of lung cancer is surgical resection, and neoadjuvant chemotherapy modality is also available. In case of complete resection, postoperative adjuvant chemotherapy is recommended.
In the 97th stage of lung cancer, T4 means that the primary tumor cannot be resected. However, if the satellite lesion is located in the lung lobe where the primary cancer is located, there is no technical problem with surgical resection, a situation that is clearly inconsistent with the definition of T4 in the 97 staging, and survival is significantly higher than in the traditionally defined T4 group. Several surgical series case reports emphasize that the survival of lung cancer in this situation is in fact not different from that of stage IIIA.
(2) For other resectable T4No-1 stage IIIB non-small cell lung cancer, neoadjuvant chemotherapy may be preferred, as appropriate, or surgical resection may be an option. In case of complete resection, postoperative adjuvant chemotherapy is considered. If the margins are positive, postoperative radiotherapy and platinum-containing regimen chemotherapy are recommended.
Some T4 lung cancers invading mediastinal structures such as the ramus, superior vena cava, and atrium still have the opportunity for surgical resection, but the indications should be strictly controlled. Lung cancer with invasion of the ramus, whether submucosal or extrabronchial, used to be considered unresectable, but now it is possible to perform total pneumonectomy with tracheal ramus resection and direct anastomosis of the main bronchus on the opposite side of the trachea (sleeve total pneumonectomy). Limited invasion of the atrial wall can often be completely removed, and a few patients can expect long-term survival. A summary of 8 studies of 327 aortic resections from 1980 to 2000 showed that the operative mortality rate for aortic resection was 18% and the 5-year survival rate was 26%, while the 5-year survival rate for resection of other T4 structures was about 15%.
(3) In unresectable T4No-1, stage IIIB non-small cell lung cancer, the current standard mode of treatment is a combination of platinum-containing regimen chemotherapy and radiation therapy. The recommended regimen is a pegylated glycoside + cisplatin regimen combined with radiation therapy followed by 3 cycles of docetaxel for consolidation chemotherapy.
(4) For T4 stage IIIB non-small cell lung cancer with pleural effusion, if the pleural effusion examination is negative for several times, the treatment will be according to TNM stage; if positive, the treatment will be according to stage IV non-small cell lung cancer, and local treatment of the chest cavity will be added if necessary.
4.Optional chemotherapy regimens for locally advanced NSCLC
(1) The alternative second-generation platinum-containing chemotherapy regimens for locally advanced NSCLC are EP, VP, MIP, etc.
(1) Second generation platinum-containing chemotherapy regimens available for locally advanced NSCLC are EP, VP, MIP, etc. (2) The third-generation platinum-containing chemotherapy regimens available for locally advanced NSCLC are GP, DP, TP, NP, etc.
5.Radiation therapy for locally advanced NSCLC
(1) Hyper-segmentation radiotherapy (HRT) only improves the local control rate and survival rate of favorable NSCLC.
Favorable type NSCLC refers to stage IV non-small cell lung cancer with KPS ≥ 70 and weight loss2 in the 6 months before treatment, which can be treated with best supportive therapy as appropriate.
Results from 10 studies with a total of 12,419 cases showed
PS is the most important impact factor of chemotherapy, and patients with PS >2 rarely receive a survival benefit from chemotherapy or even symptomatic improvement. Optimal supportive therapy includes palliative radiotherapy, appetite promotion (megestrol, etc.), nutritional support, electrolyte correction, morphine-based analgesic therapy and psychosocial support.
(E) Retreatment of recurrence and metastasis after treatment
Non-small cell lung cancer that has recurred or metastasized after treatment should be further grouped according to PS status. Patients with good functional status should be considered for systemic chemotherapy or targeted therapy; those with poor functional status should be given targeted therapy or optimal supportive therapy. Based on systemic treatment, appropriate local treatment should be selected for specific local conditions in order to improve symptoms and quality of life.
1.For local recurrence of bronchial obstruction causing dyspnea, treatment options include laser/stenting/surgery; brachytherapy; external radiation therapy; photodynamic therapy.
2.For local recurrence of superior vena cava obstruction, external irradiation radiotherapy or internal stenting of superior vena cava may be considered.
3.Local recurrence of resectable, consider re-surgical resection or external irradiation.
4. Severe hematochezia caused by local recurrence can be considered external radiation radiotherapy; brachytherapy; laser therapy; photodynamic therapy; bronchial artery embolization; surgery.
5. Palliative whole brain radiation therapy can be considered for multiple brain metastases.
6. Palliative external irradiation therapy and bisphosphonate drug therapy can be considered for systemic bone metastases, and orthopedic fixation can be used if necessary.
7.Distant metastases with local symptoms can be considered for local palliative external irradiation.
8.Surgical resection or external irradiation can be considered for isolated metastases.
Section 2: Staged comprehensive treatment of small cell lung cancer
(I) Treatment of limited stage small cell lung cancer
1. For limited-stage small cell lung cancer with clinical stage cTl-2N0 workup, lobectomy + mediastinal lymph node dissection is recommended. For those who are still pN0 after surgery, 4-6 cycles of EP regimen chemotherapy is recommended; for those who are pN+, systemic chemotherapy is recommended along with radiation therapy to the mediastinal fields.
Less than 10% of limited-stage small cell lung cancers diagnosed clinically as stage I have a 5-year survival rate of 35% to 40% with postoperative chemotherapy. In case of preoperative chemotherapy, the 5-year survival rate can be 35% to 65%. A retrospective study of 1260 cases of SCLC by Dongfu Chen et al. showed that the effect of surgery + radiotherapy ten chemotherapy group was significantly better than other treatment groups, and the multifactorial analysis was statistically significant.
2, The treatment mode of concurrent chemoradiotherapy is recommended for cTl-2 N0 limited stage small cell lung cancer that is not suitable for surgery.
3, For limited-stage small cell lung cancer other than cTl-2 N0, chemotherapy is preferred if PS2, plus radiation therapy if necessary.
Meta-analysis of 2103 cases showed that chemotherapy plus chest radiotherapy reduced the local recurrence rate by 25%-30%, decreased the mortality rate by 14%, and increased the 2-year overall survival rate by 5%-7% compared with chemotherapy alone.
4, EP regimen can be cisplatin + pedialyte glycoside or carboplatin + pedialyte glycoside, if combined with radiation therapy, cisplatin + pedialyte glycoside is recommended.
EP regimen has a response rate of 80%-100% and a complete remission rate of 50%-70%, thus becoming the most commonly used chemotherapy regimen for limited-stage small cell lung cancer.
5. Concurrent chemoradiotherapy modality is superior to sequential chemoradiotherapy modality, and radiation therapy is recommended to be started in the first or second cycle of chemotherapy.
Two randomized controlled studies have compared the timing of radiation therapy intervention in concurrent chemoradiotherapy and found that concurrent radiation therapy in the first or second cycle of chemotherapy is better than using radiation therapy in the sixth cycle of chemotherapy in reducing the local recurrence and distant metastasis rates and improving the survival rate.
6. The radiation therapy dose schedule can be 1.5 Gy twice a day for a total dose of 45 Gy or 1.8 Gy once a day for a total dose of at least 54 Gy.
The ECOG/RTOG (the Eastern Cooperative On-cology Group/Radiation Therapy Oncology Group) study showed that the median survival time was 23 months versus 19 months for twice-daily radiation therapy versus once-daily radiation therapy.
7. For limited-stage small cell lung cancer in complete remission, prophylactic whole-brain irradiation is recommended at a dose of 24 Gy/8 to 36 Gy/18 times.
A 1999 Meta-analysis, which pooled seven randomized controlled studies with a total of 987 cases, concluded that prophylactic brain irradiation reduced the risk of death by 16% (RR 0.84, 95% CI 0.73-0.97), increased the 3-year survival rate from 15% to 21%, reduced the incidence of brain metastases, and improved overall survival and tumor-free survival in limited-stage small cell lung cancer in complete remission. The 3-year survival rate was improved from 21%, which reduced the incidence of brain metastasis and improved the overall survival and tumor-free survival of small cell lung cancer in complete remission.
8. Rescuing surgical resection may be helpful in limited-stage small cell lung cancer that has not achieved complete remission after conventional chemoradiotherapy.