DIAGNOSTIC AND THERAPEUTIC PROCEDURES FOR LUNG CANCER AND FOR DISEASES OF THE RESPIRATORY SYSTEM
INTERVENTIONAL PNEUMOLOGY
Interventional Pneumology is a branch of pneumology that uses minimally invasive techniques for the diagnosis and treatment of patients suffering from respiratory diseases, including lung cancer. At the IEO, an outpatient clinic of interventional pulmonology offers state-of-art minimally invasive procedures for patients requiring a preliminary evaluation, before surgical procedures are performed. The IEO interventional pneumology program started in 2010, to provide a diagnostic and therapeutic service at the forefront of pulmonary medicine. The Division of Interventional Pneumology annually performs more than 700 operational bronchoscopy procedures for the diagnosis and treatment of lung cancer patients. The interventional pulmonologists work within the Thoracic Surgery Division and collaborate with many specialists (radiation oncologists, medical oncologists and other surgical specialties) for the diagnosis and treatment of lung cancers.
EBUS-TBNA (TRANS-BRONCHIAL ULTRASOUND)
EBUS (Endo-bronchial Ultrasound) is a minimally invasive bronchoscopy technology that allows the respiratory specialist to visualize the central structures of the mediastinum and peripheral lung parenchyma, otherwise not accessible with traditional bronchoscopy, using an ultrasound probe.
EBUS is used in many suspected or confirmed cases of lung cancer for the evaluation of lung nodules and/or enlarged mediastinal lymph nodes and for the diagnosis of benign pulmonary and mediastinal diseases such as thymomas, tuberculosis and sarcoidosis. In Thoracic Oncology, EBUS is a useful tool for mediastinal staging, to further guide treatment decision-making.
The procedure does not require general anesthesia and is performed under sedation by the anesthesiologist, to ensure safety alongside avoiding patient discomfort during the procedure.
EBUS significantly increases the diagnostic accuracy of transbronchial biopsies under fluoroscopic guidance and transbronchial needle aspiration.
At the IEO, EBUS-TBNA bronchoscopies are performed in collaboration with a pathologist in the endoscopy room, who can provide immediate evaluation of the sample material (ROSE: Rapid on-site cytologic Evaluation). EBUS-TBNA is also an excellent method to obtain new tissue biopsies in cancer patients, to improve the disease histological and molecular characterization.
RIGID BRONCHOSCOPY
Rigid bronchoscopy is performed under general anesthesia, to obtain the clearance of major airways, such as the trachea and main bronchi, that may have been obstructed by intra-luminal lung cancer, thereby restoring their patency. Lesions are typically mechanically removed or treated with laser therapy. For patients with intra-luminal lesions resistant to complete recanalization or experiencing trachea-bronchial tree distortion due to extrinsic compression, endo-bronchial stents may be strategically placed for palliative purposes.
PLEURAL MEDICAL INSPECTION
Pleuroscopy plays a pivotal role in thoracic oncology by providing minimally invasive access to the pleural cavity for diagnostic and therapeutic interventions. Through a small incision, a thin, flexible tube with a camera attached (pleuroscope) is inserted, enabling visualization of the pleura and associated structures. This procedure aids in obtaining biopsies of pleural lesions, staging of lung cancer, and assessing pleural effusions. Additionally, pleuroscopy allows for the instillation of medications directly into the pleural space and the drainage of fluid or air, contributing to improved patient outcomes and management of thoracic malignancies.
CHEST COMPUTED TOMOGRAPHY (TC)
Chest computer tomography (CT) is crucial in lung cancer diagnosis, as it offers detailed images of the lungs and surrounding structures. It can be used to detect tumors, determining their size, location and spread, to further guide treatment decisions, disease monitoring and response to therapy.
The CT scan of the brain and the abdomen completes staging, to determine the presence of suspected distant metastases.
POSITRON EMISSION TOMOGRAPHY (PET)
Positron emission tomography (PET) with 18-fluorodeoxyglucose (18-FDG) is pivotal in lung cancer diagnosis and monitoring treatment response as it provides functional imaging by detecting metabolic activity. PET scans can distinguish between benign and malignant lesions, identify distant metastases and aid in staging lung cancer, guiding treatment decisions for optimal patient management.
FINE-NEEDLE ASPIRATION/TRANS-THORACIC BIOPSY
CT-guided fine needle aspiration biopsy and transthoracic biopsy are particularly useful when the lesion is accessible from the outside of the chest wall.
DIAGNOSIS OF NON-SMALL CELL LUNG CANCER
The diagnostic process for a pulmonary nodule typically involves several steps to determine the nature of the nodule and whether it is benign or malignant. According to national and international guidelines, the diagnostic workflow commonly includes:
- Clinical evaluation: a detailed medical history and a complete physical examination allow to assess the patient's overall health and identify any risk factors for lung cancer, such as smoking history or exposure to environmental toxins.
- Multidisciplinary discussion: the collaboration between multiple healthcare professionals ensures an accurate diagnosis and the appropriate management plan for each patient.
- Imaging studies: computed tomography (CT) scans are often performed to detect and evaluate pulmonary nodules. CT scans provide detailed images of the lungs and can help determine the size, location, and characteristics of the nodule.
- Further imaging: if the initial imaging studies reveal a suspicious nodule, additional imaging tests such as positron emission tomography (PET) scans may be performed to assess the metabolic activity of the nodule and its potential for malignancy.
- Cardio-pulmonary function tests: also known as pulmonary function tests (PFTs), assess how well the lungs and heart are functioning together to provide oxygen to the body and remove carbon dioxide.
- Biopsy: if the imaging studies suggest that the nodule may be cancerous, a biopsy may be performed to obtain a tissue sample for further analysis. Biopsy techniques may include bronchoscopy (using a thin, flexible tube inserted into the airways) or needle biopsy (using a needle inserted through the chest wall) or surgical biopsy (removing a tissue sample during surgery under general anesthesia through a minimally invasive video-assisted technique).
- Pathological evaluation: the tissue sample obtained during the biopsy is examined by a pathologist under a microscope to determine whether the nodule is benign or malignant. This evaluation may also include molecular testing to identify specific genetic mutations associated with lung cancer.
- Follow-up imaging: If the nodule is determined to be benign, regular follow-up imaging may be recommended to monitor for any changes in size or appearance. If the nodule is malignant, further tests may be performed to determine the stage of the cancer and develop an appropriate treatment plan.
Surgical biopsy for suspected lung cancer may be indicated in cases where less invasive procedures, such as bronchoscopy or needle biopsy, yield inconclusive results or provide inadequate tissue samples for analysis. Additionally, surgical biopsy may be considered when the suspected lung nodule is located in a challenging or inaccessible area, or if it is too small to be sampled safely using less invasive techniques. In such cases, an intraoperative pathology evaluation is performed to obtain histological diagnosis and, in case lung cancer is confirmed, surgery is performed. Ultimately, the decision to perform a surgical biopsy is based on various factors and is typically made by the multidisciplinary team.
TREATMENT STRATEGIES FOR EARLY NON-SMALL CELL LUNG CANCER
Surgical treatment options for early-stage non-small cell lung cancer (NSCLC), namely stage I-II NSCLC, typically involve the removal of the tumor and surrounding tissue through surgery. The main surgical approaches for early-stage NSCLC, either performed through video-assisted thoracoscopy (VATS) or thoracotomy, include:
- Lobectomy: it involves the removal of the entire lobe of the lung containing the tumor. A lobectomy is often recommended when the tumor is localized in one lobe, or two lobes (bi-lobectomy), and can be safely removed while preserving adequate lung function.
- Segmentectomy: in cases where the tumor is small and located in a specific segment of the lung. This procedure involves removing only the affected segment of the lung while preserving the rest of the lung tissue. Segmentectomy may be considered when preserving lung function is particularly important, such as in patients with limited lung reserve or compromised pulmonary function.
- Wedge resection: it can be considered for very small tumors or patients with limited lung function who may not tolerate more extensive surgery. This procedure involves removing only the tumor and a small margin of surrounding healthy tissue.
- Pneumonectomy: in rare cases where the tumor involves the entire lung or is located centrally and cannot be removed with a lobectomy or segmentectomy, a pneumonectomy may be necessary. This procedure involves removing the entire lung affected by cancer and can be associated with a higher risk of complications and reduced lung function compared to other surgical approaches. It is typically reserved for selected patients, when no other options are feasible.
- Sleeve resection, also known as bronchial sleeve resection or bronchoplasty: it is typically performed when the tumor or lesion is located near the main bronchus and involves a segment of the bronchial wall and requires the removal of a portion of a damaged segment of the main bronchus while preserving the continuity of the airway. This procedure preserves as much lung tissue and function as possible while effectively treating conditions such as lung cancer, bronchial stenosis (narrowing of the bronchus), or bronchiectasis (chronic dilation of the bronchial tubes). Benefits of sleeve resection include preservation of lung function, reduced risk of postoperative complications compared to more extensive lung resections, and improved quality of life.
The choice of the surgical approach depends on factors such as the size and location of the tumor, the patient's overall health and lung function, and the goals of the treatment. It is important for patients to discuss the potential risks and benefits of each surgical option with their healthcare team to determine the most appropriate treatment plan for their individual circumstances.
Lymphadenectomy, also known as lymph node dissection, is a surgical procedure performed during surgery to remove lymph nodes in the mediastinum (the area between the lungs) and assess whether cancer has spread to these lymph nodes. The role of lymphadenectomy in NSCLC surgery is multifaceted and includes accurate disease staging, prognostic evaluation and reducing the risk of locoregional recurrence while improving the chances of long-term disease control.
Patients undergoing lung cancer surgery with a curative intent must undergo pulmonary function tests prior to treatment as well as cardiac and anesthesia assessments in order to exclude from surgery those patients that could be at high risk of developing severe consequences after thoracic surgery.
The treatment of stage IIIA NSCLC requires a multidisciplinary approach with the collaboration of thoracic surgeons, medical oncologists, radiation oncologists and pneumologists:
- Chemoradiotherapy (CRT): concurrent CRT involves the administration of chemotherapy along with radiation therapy, typically delivered simultaneously over several weeks. Chemotherapy helps to sensitize the cancer cells to the effects of radiation, leading to improved tumor control. Chemoradiotherapy may be followed by consolidation immunotherapy in selected patients.
- Surgery followed by adjuvant therapy: For selected patients with resectable stage IIIA NSCLC, surgery may be performed, followed by adjuvant therapy to reduce the risk of disease recurrence. Adjuvant therapy may include chemotherapy, radiation therapy, targeted therapy, immunotherapy or a combination of them, depending on the extent of lymph node involvement, molecular biology and other risk factors. Patient’s selection is required.
- Neoadjuvant therapy followed by surgery: In some cases, neoadjuvant therapy (chemotherapy or chemoradiotherapy given before surgery) may be recommended to downstage the tumor and improve the chances of successful surgical resection. Neoadjuvant therapy may be followed by surgery to remove the remaining tumor and involved lymph nodes.
TREATMENT STRATEGIES FOR LOCALLY ADVANCED, NON-RESECTABLE NON-SMALL CELL LUNG CANCER
The treatment of locally-advanced non-resectable non-small cell lung cancer (NSCLC) typically involves a combination of chemotherapy, radiation therapy, and in some cases immunotherapy upon completion. The goal of treatment is to control the growth of the cancer, alleviate symptoms, and improve overall survival. Here are the main treatment modalities for locally-advanced non-resectable NSCLC:
- Chemoradiotherapy (CRT): Concurrent chemoradiotherapy is considered the standard approach and involves the administration of chemotherapy along with radiation therapy, typically delivered simultaneously over several weeks. Chemoradiotherapy may be followed by consolidation immunotherapy in some cases.
- Radiation therapy: External beam radiation therapy (EBRT) is commonly used to deliver high-dose radiation to the tumor and nearby lymph nodes. It may be given alone or in combination with chemotherapy. Stereotactic body radiation therapy (SBRT) or stereotactic ablative radiotherapy (SABR) may also be considered for selected patients with limited metastatic disease or oligometastases.
THERAPY OF ADVANCED NON-SMALL CELL LUNG CANCER
Overall, the treatment landscape for NSCLC is characterized by personalized, multimodal, and innovative approaches aimed at maximizing therapeutic efficacy, minimizing treatment-related toxicities, and improving survival outcomes for patients across all stages of the disease. Rapid advancements in precision medicine and immunotherapy hold promise for further improving the prognosis and quality of life for individuals with NSCLC.
Molecular and PD-L1 testing plays a central role in the personalized management of NSCLC (see Thoracic Oncology, Treatment of Lung Cancer). Indeed, it allows a more specific treatment selection, predicting treatment response, monitoring treatment resistance, and providing valuable prognostic information. Incorporating molecular testing into routine clinical practice enhances treatment decision-making, improves patient outcomes, and contributes to the advancement of precision medicine in NSCLC care.
ROLE OF RADIOTHERAPY IN NON-SMALL CELL LUNG CANCER
Overall, the decision to include radiotherapy as part of the treatment plan in NSCLC depends on factors such as tumor size, location, histology, disease stage, patient comorbidities and treatment goals.
- Definitive (curative) radiotherapy: for patients who are not candidates for surgery due to comorbidities, poor lung function, or patient preference, definitive radiotherapy may be used as the primary treatment. High-dose radiation therapy is delivered to the tumor and surrounding tissues with the goal of eradicating cancer cells while preserving normal lung function. Definitive radiotherapy may be delivered alone or in combination with chemotherapy (concurrent chemoradiotherapy) for enhanced tumor control.
- Adjuvant radiotherapy: in selected cases where surgery has been performed but there is a high risk of local recurrence, adjuvant radiotherapy may be recommended to reduce the risk of recurrence and improve long-term disease control. Adjuvant radiotherapy is typically delivered to the surgical bed and regional lymph nodes to target any residual cancer cells that may remain after surgery.
- Palliative radiotherapy: in cases where the tumor is causing symptoms such as pain, dyspnea (difficulty breathing), or hemoptysis (coughing up blood), palliative radiotherapy may be used to alleviate symptoms and improve quality of life. Radiotherapy can be used to treat symptomatic bone metastases and brain metastases.
THERAPY OF SMALL CELL LUNG CANCER
SCLC is often aggressive and tends to spread quickly to other organs, therefore treatment is usually aimed at controlling the disease and alleviating symptoms. The choice of treatment for SCLC depends on factors such as the stage of the disease, tumor size and location, overall health and functional status of the patient, and treatment goals.
For patients with limited-stage small cell lung cancer (SCLC), which is confined to one side of the chest and can be encompassed within a tolerable radiation field, the treatment typically involves a combination of chemotherapy and thoracic radiation therapy. The goal of treatment is to achieve local control of the disease, prevent distant metastasis, and improve overall survival.
- Chemotherapy, most commonly platinum-based chemotherapy (such as cisplatin or carboplatin) in combination with etoposide. Chemotherapy is usually administered intravenously in cycles over a period of several weeks, with rest periods in between to allow the body to recover from treatment-related side effects.
- Thoracic radiation therapy: Concurrent thoracic radiation therapy is typically administered along with chemotherapy for patients with limited-stage SCLC. Radiation therapy is delivered to the primary tumor in the lung as well as any involved lymph nodes in the chest. The goal of radiation therapy is to shrink the tumor, prevent local recurrence, and improve overall disease control. Radiation therapy may be given using external beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT), depending on the size and location of the tumor.
Prophylactic cranial irradiation is a type of radiation therapy that may be recommended for patients with limited-stage SCLC who have had a good response to initial treatment. PCI involves delivering low-dose radiation to the brain to reduce the risk of developing brain metastases, which are common in SCLC. PCI has been shown to improve overall survival and reduce the incidence of brain metastases in patients with limited-stage SCLC.
For patients with extensive-stage small cell lung cancer, which has spread beyond one side of the chest to distant sites in the body, the treatment typically involves systemic chemotherapy in combination with immunotherapy along with supportive care to manage symptoms and improve quality of life. Unlike limited-stage SCLC, the treatment approach for extensive-stage SCLC is focused on controlling the spread of the disease and alleviating symptoms.
LOCO-REGIONAL TREATMENT AND OTHER TREATMENTS FOR LUNG CANCER METASTASES
Beyond palliative radiotherapy, surgical approaches can be considered for the treatment of contralateral lung, bones and other metastatic sites, provided that these indications are discussed within a multidisciplinary team.
Furthermore, systemic treatments for extensive bone lesions are available and can be discussed with the medical team, when indicated.