Most lung cancers are now advanced and can only be treated palliatively, resulting in a very short survival time. There are many reasons for the late detection of lung cancer, but the main reason is the lack of effective early diagnosis methods for high-risk groups. Early stage tumors with microinvasive carcinoma in situ have nearly 100% chance of cure. If lung cancer could be diagnosed more often at an early stage in clinical practice, it would significantly improve patient prognosis and increase patient survival. For this reason, new methods for early diagnosis of lung cancer need to be continuously improved and developed.
Routine screening methods for CT examination of peripheral lung cancer
Most of the current trials have concluded that the role of CT in early diagnosis of lung cancer is positive. 7 clinical trials have shown that CT has a good stability in detecting early lung cancer, with a 71%-100% detection rate of stage I lung cancer. Another 2 clinical trials showed an overall long-term survival rate of greater than 71% for lung cancer and a 92% survival rate for stage I lung cancer diagnosed by CT. However, some small studies have shown that CT, while improving the detection rate of early lung cancer, is not significant in reducing lung cancer mortality. This may be related to the inability of annual CT examinations to detect lung cancers that grow rapidly and metastasize at an early stage. However, recent clinical trials have shown that CT can diagnose lung cancer up to one year earlier than chest radiographs, with an additional 0.019 years of survival per CT examination and an overall 15% reduction in mortality, while annual CT screening can reduce lung cancer mortality by 23%. Currently it is mostly believed that low-dose CT its similar to regular CT in early diagnosis of lung cancer, and there may be definite results about LDCT to reduce lung cancer mortality after the conclusion of the US NLST trial and the Dutch-Belgian NELSON trial.
Although CT screening for lung cancer remains controversial, it remains the simplest and most effective method to screen for peripheral lung cancer and reduce lung cancer mortality until large-scale randomized clinical trials become available. However, central lung cancer is not easily detected by modern radiological methods, and bronchoscopy, as an invasive test, is not suitable for screening, so new screening methods need to be developed.
CT remains the simplest and most effective method to screen for peripheral lung cancer and reduce lung cancer mortality.
The sensitivity, specificity and accuracy of CT scan fusion imaging for lung cancer diagnosis can reach about 85%, which greatly exceeds that of conventional CT, and has important value in the differentiation of lung cancer staging and whether there is distant metastasis, but its expensive price and false-positive rate of about 10% limit the wide application of PET-CT.
Endobronchial ultrasound helps in the diagnosis of early lung cancer staging
CT and MRI scans are unable to achieve precise staging of lung cancer, and external ultrasound is also unable to examine the paratracheal and hilar regions when staging mediastinal and parabronchial structures, and transesophageal ultrasound is unable to examine the anterior trachea, the right side of the hilum and its anterior structures. The establishment of the acoustic anatomy of the airway and mediastinal structures has made it possible to apply endobronchial ultrasound.
EBUS is performed in two ways: a rotational transducer at the tip of the bronchoscope, which provides images along the long axis of the bronchoscope at 36 degrees, and a linear transducer at the tip of the bronchoscope, which provides images parallel to the long axis at 50 degrees.
EBUS is useful for three main reasons.
1. To increase the positive rate of isolated lung nodule biopsies.
Studies have shown that EBUS increases the positivity rate to over 70% when biopsies of isolated pulmonary nodules <2 cm are performed using a rotating sensor, much higher than conventional bronchoscopy. EBUS also has a higher positive rate than conventional blind transbronchial needle aspiration biopsy (TBNA) in the examination of mediastinal and hilar nodules.
2. Increase the positive rate of general TBNA for hilar and mediastinal lymph node biopsies to better stage lung cancer and thus guide treatment.
EBUS can detect lymph nodes as small as 2-3 mm under appropriate conditions. In addition, EBUS combined with TBNA can localize lymph nodes as small as 8 mm or less, improving diagnosis and reducing complications.
Mediastinal lymph node staging determines the treatment strategy and prognosis of patients with non-small cell lung cancer. One study used EBUS to correctly examine mediastinal lymph node staging in 172 patients in 207 with a mean lymph node size of 1.7 cm. EBUS can also be used for lymphatic biopsy sampling in PET-positive mediastinal lymph nodes. the combination of EBUS and ultrasound endoscopy allows for the puncture of most mediastinal lymph nodes.
3. Increase the detection rate of early endobronchial tumors and perform local treatment.
EBUS can detect endobronchial tumors that cannot be detected by CT. The pathological anatomical definition of early tumors is that the tumor does not extend beyond the submucosa. When the mucosa is altered, or even when the mucosa appears to be intact, EBUS can detect the altered acoustic anatomy and sometimes the submucosal infiltration of the tumor. In addition, EBUS can examine the extent of tumor infiltration and treat carcinoma in situ. A study from Japan showed that EBUS correctly detected the depth of tumor infiltration in 23 of 24 patients with lung cancer, with significantly higher sensitivity specificity than CT. Photodynamic therapy was administered to 18 of these patients with early-stage NSCLC or 9 with carcinoma in situ, and no tumor recurrence was detected at the subsequent 32-month follow-up.
The results of a randomized prospective study showed that the combination of fluoroscopy and EBUS significantly improved the differential diagnosis of benign and malignant lesions in the bronchial wall. Further prospective studies will be devoted to comparing EBUS with conventional methods and improving including Doppler sonoanatomy, computational tissue analysis and adding biopsy. As multifaceted studies are conducted, EBUS has the potential to become routine in the future, providing an important aid to diagnosis and interventional fibrinoscopy. It is often too late to diagnose lung cancer by X-ray examination of lung shadows.
Fluorescence confocal microscopy
Although self-fluorescence ciliofluorescence microscopy can detect more early endobronchial tumors, its specificity is still low, with some reports suggesting only 25%-50%. Therefore, in recent years, fluorescence confocal microscopy has been developed to obtain microscopic images of living tissue by fitting a 1-mm fiberoptic probe into the working channel of the bronchoscope. The signal of FCFM mainly comes from the elastin component of the basement membrane area. In vivo trials have demonstrated that FCFM accurately diagnosed 19 of 22 patients with bronchial chemosis or dysplasia and accurately detected all 5 patients with carcinoma in situ and 2 patients with invasive carcinoma. The combination of fluorescence confocal microscopy and bronchoscopy allows observation of changes in the bronchial basement membrane associated with precancerous lesions, even in situ carcinoma, with minimal tissue damage. This technique can also be used to visualize airway remodeling in asthma and chronic obstructive pulmonary disease.
Cellular and molecular biology
In sputum examination, only direct results based on morphological methods can provide important input for diagnosis. For example, the difference between squamous cell metaplasia and dysplasia can be identified only by cytopathological examination.
Currently, new sputum examinations include.
1, liquid-based thin-layer cytology filming technique, which can significantly improve the detection rate of malignant cells compared with conventional sputum examination.
2. 24-hour sputum coagulation sedimentation section, which has a significantly better positive rate than sputum smear, while the combined test of sputum smear and 24-hour sputum coagulation sedimentation section has a higher positive rate.
In addition, automated sputum cell analyzers have been used in prospective studies to screen for malignant lesions combined with changes in nuclear DNA content. The results suggest that automated sputum cell analysis can be used as a non-invasive and sensitive method to detect malignant changes in sputum, providing a first diagnosis of the presence or absence of a tumor. In addition, it is possible to combine certain well-defined molecular biology markers with automated sputum cell analysis in the future to screen for lung cancer in high-risk populations.
Molecular biology methods are used to detect genetic and molecular alterations in the early stages of lung cancer. Commonly used detection techniques include polymerase chain reaction, reverse transcription polymerase chain reaction and gene chip technology, which have been widely applied to sputum, bronchial brushings, bronchoalveolar lavage fluid, tissue biopsies, peripheral blood and bone marrow specimens.
Molecular examination of lung cancer includes a variety of lung cancer molecular markers, such as K-ras and p53 mutations and p16, hypermethylation of RASSF1A and NORE1A, telomerase activity, inhomogeneous riboprobes, and microsatellite abnormalities. It was found that p53 mutations and p16 hypermethylation may be promising indicators for sputum screening. In sputum cytogenetic examination, sputum tobacco-associated deletion of HYAL2 and FHIT genes may be used as screening indicators for early lung cancer. However, it is too early for these tests to be applied clinically.
Review and Analysis
With the advancement of new screening and detection methods for early lesions, the results of these methods have proven promising, and autofluorescence, EBUS, fluorescence confocal, and electromagnetic navigation bronchoscopy will be increasingly used in the clinic. And, in the near future, more efforts will be made to further improve and develop other new methods, such as molecular markers for optimal phase-reference stratification. In addition, to be able to detect lesions earlier, we need a deeper understanding of the natural history of lung cancer, which will help us in prevention or genetic repair.