The Office of Oncology Prevention and Control of the Ministry of Health released the latest warning in the National Cancer Control Strategy Study Report: Lung cancer is the number one cancer in China, with the incidence and mortality rate of lung cancer taking the first place among men.
There are 350 million smokers in China, and with the aging population, accelerated urbanization, and increasingly serious air and environmental pollution, the incidence and mortality rate of lung cancer will continue to increase and has become a major health concern for the whole society. The prognosis of lung cancer is closely related to the stage at the time of clinical diagnosis. The 5-year survival rate of stage I lung cancer patients after surgery is 60%-70%, while the 5-year survival rate of stage II-IV lung cancer after surgery decreases from 40% to 5%. Therefore, striving for “early detection, early diagnosis and early treatment” is an important measure to reduce lung cancer mortality.
Screening for lung cancer with low-dose spiral CT
The results of the International Early Lung Cancer Action Plan (I-ELCAP) showed that 85% of lung cancers detected by low-dose spiral CT during annual physical exams are clinical stage I lung cancers, and the 5-year survival rate of early lung cancers detected by screening can be more than 90% after surgical treatment. The recently published results of the National Lung Cancer Screening Trial (NLST) showed that the use of low-dose spiral CT scans for lung cancer screening reduced lung cancer mortality by 20% compared to X-ray chest radiographs, which is equivalent to the number of all deaths from breast cancer.NLST data showed that the use of regular screening with X-ray chest radiographs and sputum cytology failed to reduce lung cancer mortality. CT is more effective in detecting small nodular lesions in the peripheral lung than plain X-rays, and is 10 times more effective than plain X-rays in detecting small nodules in the lung. Studies have confirmed that low-dose spiral CT can detect more curable early-stage lung cancers than the previously used chest X-ray plus sputum cytology.
Most of the lung cancers detected by low-dose spiral CT screening are early peripheral lung cancers with no clinical symptoms, while early central lung cancers can show respiratory symptoms such as irritating cough or blood sputum or even coughing up blood in the early stage of the disease. For such patients, early diagnosis using sputum thin-layer liquid-based cytology and fiberoptic bronchoscopy, especially fluoroscopic endoscopy, is particularly important.
The development of lung cancer is closely related to lifestyle. Tobacco has been shown to be a major carcinogenic factor in the development of lung cancer, and approximately 90% of lung cancers are thought to be caused by smoking. The risk of lung cancer in heavy smokers (25 or more cigarettes per day) is 50 times higher than in nonsmokers. Experience in Europe and the United States has shown that effective tobacco control policies can lead to a reduction in smoking rates throughout society, which in turn leads to a reduction in lung cancer incidence and mortality.
Minimally invasive surgical treatment of early-stage lung cancer
Lung cancer surgical treatment has made significant progress in recent years, and the most representative one is the emergence and popularity of minimally invasive thoracic surgery techniques. Minimally invasive thoracic surgery mainly includes three types of surgical procedures, namely thoracoscopic surgery (VATS), thoracoscopic-assisted small-incision Hybrid surgery, and minimally invasive muscle non-invasive open thoracotomy (MST). In the United States, thoracoscopic lobectomy accounts for more than 20% of all lobectomies.
Peripheral non-small cell lung cancer (NSCLC) in clinical stage I is currently considered the best indication for VATS, with no significant differences in operative time, intraoperative bleeding, or number of intraoperative lymph nodes dissected compared to conventional open-heart surgery. The postoperative rates of pulmonary and cardiovascular complications were significantly lower than those of conventional open-heart surgery, and the number of days of postoperative chest closed drainage tube retention and hospital stay were also significantly shorter than those of conventional open-heart surgery.
On the other hand, there was no significant obstacle to coughing and sputum removal, and the lung function recovered faster after surgery. The results of a multi-center clinical study led by the Lung Cancer Treatment Center of Capital Medical University in China and the United States showed that the number of days of hospitalization after VATS was shorter than that of traditional open-heart surgery, and the time to start adjuvant chemotherapy was significantly earlier than that of open-heart surgery, and the completion rate of adjuvant chemotherapy was significantly higher.
VATS lobectomy for early-stage lung cancer has been widely performed in major medical centers in China, and each center has developed its own unique thoracoscopic lobectomy approach based on the configuration of thoracoscopic instruments, the technical training experience and proficiency of the surgeon, and the different affordability of the patients in the region: for example, the “one-way” approach represented by Liu Lunxu of West China Hospital The “one-way” operation represented by Liu Lunxu of West China Hospital, the “single-operating hole” operation represented by Chu Xiangyang of PLA General Hospital, and the “Wang’s technique” represented by Wang Jun of Peking University People’s Hospital, etc.
With the increasing skill, experienced thoracic surgeons are able to perform more complex thoracic surgeries such as bronchial sleeve lobectomy, pulmonary artery and other large vessel resection and reconstruction by using minimally invasive thoracoscopic techniques. Scholars in China have started to try to expand the indications for minimally invasive thoracoscopic surgery to clinical stage II and III NSCLC, and useful attempts have been made in Taiwan and Guangzhou to complete thoracoscopic lobectomy under epidural anesthesia.
It should be soberly recognized that VATS lobectomy only changes the surgical approach (surgical approach) of lung cancer, but the surgical treatment outcome of lung cancer is not significantly improved as a result. The current evidence-based medical evidence shows that the efficacy of VATS lobectomy for clinical stage I peripheral NSCLC is equivalent to that of conventional open surgery. Therefore, VATS lobectomy should be applied with caution to clinical stage III NSCLC with hilar lymph node metastasis, especially mediastinal lymph node metastasis.
The National Comprehensive Cancer Network (NCCN) clinical guidelines for NSCLC have recommended VATS lobectomy as the surgical treatment of choice for early-stage lung cancer since 2006, with the express caveat that the principles of surgical oncology and thoracic surgery should not be compromised at the expense of surgical quality.
Thoracoscopic-assisted small-incision Hybrid surgery requires an additional small intercostal incision, and the operator alternates between microscopic and direct vision through the propped-up intercostal space. hybrid surgery can fully combine traditional open lung resection techniques and lumpectomy techniques, greatly reducing the use of disposable instruments and effectively reducing medical costs. Currently, thoracoscopic-assisted small-incision Hybrid pneumonectomy is more commonly performed in China than VATS lobectomy. The indications, contraindications, and complications of thoracoscopic-assisted small-incision Hybrid surgery and VATS are basically the same, and when choosing between them, individualization should be emphasized to focus on patient efficacy and safety, rather than pursuing pure thoracoscopic lung resection.
Open thoracotomy without muscle damage preserves the integrity of the latissimus dorsi muscle and separates the anterior serratus muscle along the fiber direction without cutting the muscle and nerves, which significantly reduces the patient’s postoperative pain and shortens the hospital stay significantly compared with traditional open thoracotomy. Advanced surgeons skilled in this surgical technique can perform bronchial sleeveplasty, ramus resection reconstruction and superior vena cava reconstruction.
Sublobar resection for early stage I lung cancer
With the development of lung cancer screening programs and increased awareness of health checkups, especially the widespread use of spiral CT, more early stage I lung cancers can be detected clinically, especially the diagnosis of grossly opaque nodules (GGO) in the lung is increasing year by year. A comparison of the imaging and pathology of GGO as well as its clinical biological behavior revealed that this is a special type of lung cancer that is mildly invasive, less likely to metastasize, and has a very good prognosis.
Data from Japan show that limited resection (wedge resection or segmental resection) of this type of T1aN0M0 lung cancer results in a 5-year survival rate of more than 90%, with minimal local recurrence and distant metastases. In early 2011, the International Association for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS) and the European Respiratory Society (ERS) jointly published recommendations for a new classification of lung adenocarcinoma, recommending that the name of bronchoalveolar carcinoma no longer be used and that it be replaced by adenocarcinoma in situ (AIS) and, together with atypical adenomatous hyperplasia (AAH), referred to as preinfiltrative lesions. .
The Japanese Society of Clinical Oncology (JCOG) is conducting two prospective clinical studies on sublobar resection (including lung wedge resection or segmental resection) for the treatment of T1aN0M0 early peripheral lung cancer <2 cm in diameter, especially for grossly opaque lesions on imaging.JCOG 0804 is a phase II clinical study looking at lung wedge resection for pure ground-glass lesions or solid fraction JCOG 0804 is a phase II clinical study looking at the outcome of wedge resection of the lung for pure vitreous lesions or mixed vitreous lesions with a solid fraction of less than 25%.
JCOG 0802 is a phase III clinical study of partially solid vitreous lesions or solid nodules <2 cm in diameter, stratified by medical center, gender, histologic type, and lesion morphology (partially solid vitreous lesions or solid nodules), randomized to lobectomy and segmental lung resection groups, with 1100 patients scheduled for enrollment. The primary prognostic endpoint was overall survival and the secondary endpoint was post-surgical lung function.
Similarly, the ongoing CALGB 140503 study, funded by the National Cancer Institute and jointly organized by the American College of Surgeons Oncology Group (ACOSOG), the Southwestern Society of Oncology (SWOG), and the Radiation Oncology Society (RTOG), is a phase III prospective clinical study comparing lobectomy and sublobar resection for the treatment of T1aN0M0 early peripheral lung cancer <2 cm in diameter. This is also a phase III prospective clinical study comparing lobectomy with sublobar resection for T1aN0M0 early peripheral lung cancer
Although advances in minimally invasive surgical techniques have allowed some patients of advanced age and/or poor cardiopulmonary function the opportunity to undergo radical surgical treatment, there are still some patients of ultra advanced age and/or poor cardiopulmonary function who are not eligible for radical surgery. Minimally invasive physically targeted therapies have emerged in recent years to offer hope for long-term survival in these patients.
Radiofrequency ablation (RFA)
RFA is the application of ablative electrodes and percutaneous puncture under CT guidance, or during surgery or under thoracoscopy, so that the radiofrequency electrodes enter the center of solid tumor tissues, and through radiofrequency output, cause coagulative necrosis in the lesion area with a temperature of 90℃ or more, and finally form liquefied foci or fibrotic tissues, thus achieving the purpose of local elimination of tumor tissue. The clinical study on the safety and efficacy of CT-guided radiofrequency ablation for lung cancer in 300 cases in the Department of Thoracic Surgery of Xuanwu Hospital of Capital Medical University showed that 99% of the patients were able to complete the operation successfully and no treatment-related death occurred.
Some data showed that the 1-year and 2-year survival rates after radiofrequency ablation for NSCLC were 92% and 73%, respectively, and the 2-year survival rate for stage I NSCLC was as high as 92%. In addition, for lung metastases, CT-guided radiofrequency ablation has also achieved very good results: the 1-year and 2-year survival rates of lung metastases from colorectal cancer are 91% and 68%, respectively; the 1-year and 2-year survival rates of lung metastases from other malignant tumors are 93% and 67%, respectively.
For the application of CT-guided radiofrequency ablation for early-stage NSCLC, a multidisciplinary joint case discussion with the participation of thoracic surgeons is required, and CT-guided radiofrequency ablation is only applicable to elderly lung cancer patients who are not able to undergo thoracic surgery or whose cardiopulmonary function cannot tolerate surgery, and early-stage NSCLC is still the first choice for surgical treatment. To identify the pathological type and routinely detect lung cancer-related genes such as ERCC1, RRM1 and EGFR, some patients need individualized treatment combined with chemotherapy or targeted drugs after RFA in order to achieve prolonged survival.
Stereotactic body radiotherapy (SBRT)
The SBRT technique uses complex imaging of multiple fields to allow multiple fields to cross over at the tumor site to create a higher dose of radiation than conventional radiotherapy. A study at the University of Texas Southwestern Medical Center showed that SBRT improved local control and overall survival in patients with early-stage inoperable lung cancer, with a 3-year primary tumor control rate of 97.6%. However, the distant recurrence rate was higher at 22.1%, and those with non-squamous cancer and larger tumor size appeared to be at greater risk of distant recurrence. The study reported a 3-year progression-free survival rate of 48.3% and an overall survival rate of 55.8%.
SBRT is also indicated for T1aN0M0 early-stage peripheral lung cancer that is not amenable to surgery. Previous studies have found that even for clinically diagnosed T1aN0M0 early peripheral lung cancer <2 cm in diameter, the rate of lymph node metastasis confirmed by surgery is as high as about 20%, and SBRT cannot achieve treatment of regional lymph nodes, resulting in local recurrence or distant metastasis after radiotherapy in this group of patients.
Conclusion
To date, surgery remains the most effective treatment for early-stage NSCLC. Early diagnosis and early treatment are currently the most effective ways to reduce lung cancer mortality. Postoperative individualized comprehensive treatment combining chemotherapy or molecular targeted therapy through detection of lung cancer-related genes can effectively prolong patients’ postoperative survival and improve their quality of life.