Lung Cancer

Chest radiography (X-ray) is often the initial examination performed to determine the presence of suspicious pulmonary lesions. When pulmonary lesions are suspected, additional investigations should be undertaken to further evaluate their morphological characteristics and extent.

Computed tomography of the chest with contrast medium allows accurate assessment of the size and morphological characteristics of pulmonary lesions.

Morphological evaluation helps differentiate malignant lesions from pneumonia or other inflammatory conditions. It also enables assessment of the relationship between the pulmonary lesion and adjacent thoracic structures, such as the heart, great vessels, and esophagus, as well as the evaluation of possible lymph node involvement.

When lung cancer is suspected, CT imaging of the abdomen and brain should also be performed in addition to chest CT to evaluate potential extrapulmonary spread of disease.

Positron emission tomography is a diagnostic imaging technique that enables the metabolic evaluation of pulmonary lesions identified on CT scans. It uses a contrast agent different from that employed in CT imaging, namely fluorodeoxyglucose (FDG), a radiolabeled glucose analogue that is preferentially taken up by metabolically active tumor cells.

PET imaging is particularly useful for disease staging, as it helps define the extent of disease and detect involvement of distant organs. However, PET findings may occasionally be misleading, with false-positive results occurring in inflammatory conditions such as pneumonia, and false-negative results observed in certain lung cancer subtypes characterized by low FDG uptake, including low-grade neuroendocrine tumors and mucinous adenocarcinomas.

Contrast-enhanced CT scans of the brain, chest, and abdomen, together with FDG-PET imaging, are complementary investigations that provide detailed information regarding both the morphological and metabolic characteristics of pulmonary lesions, as well as possible involvement of hilar and mediastinal lymph nodes or distant organs. Although these imaging modalities cannot determine the histological nature of a pulmonary lesion, they represent an essential step in planning an appropriate biopsy procedure.

When imaging investigations such as Computed tomography or Positron emission tomography reveal a suspicious pulmonary lesion, a biopsy followed by histological examination is required to obtain tissue for microscopic analysis. This step is essential to establish the diagnosis (neoplastic or non-neoplastic lesion), define the histological subtype and biological characteristics, and guide treatment planning.

A biopsy consists of obtaining a tissue sample from the lesion for microscopic evaluation in order to confirm the presence of disease, determine its histological type, and assess the extent of involvement. Several biopsy techniques are available:

• Bronchoscopy: a thin, flexible instrument is introduced through the nose or mouth under local anesthesia to visualize the airways and obtain tissue samples for histological and cytological examination.
• Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): an endoscopic procedure performed under deep sedation that combines bronchoscopy with ultrasound guidance, allowing cytological sampling of mediastinal and hilar lymph nodes through the airway wall.
• Fine-needle aspiration and core needle biopsy: a fine needle is inserted under local anesthesia into the tumor, lymph node, or other target tissue to obtain cellular or tissue samples. The procedure is usually performed under CT or ultrasound guidance to accurately monitor needle placement.
• Thoracentesis: when pleural fluid is present, a sample may be obtained by inserting a fine needle into the intercostal space. Cytological analysis can then be performed to evaluate for the presence of malignant cells. In patients with large pleural effusions, thoracentesis may also provide symptomatic relief by improving respiratory function.
• Mediastinoscopy: a surgical procedure performed under general anesthesia in which an instrument is introduced through a small incision at the base of the neck to biopsy mediastinal lymph nodes. This examination contributes to tumor staging and helps determine whether surgical treatment is feasible.
• Video-assisted thoracoscopic surgery (VATS): a minimally invasive surgical procedure performed under general anesthesia in which a microcamera and surgical instruments are introduced through small thoracic incisions to visualize the pleural cavity and obtain tissue samples for histological examination.

Histological examination in lung cancer consists of the microscopic analysis of a tissue sample obtained by biopsy in order to determine whether the lesion is benign or malignant, identify the histological subtype (such as adenocarcinoma or squamous cell carcinoma), and define the tumor stage and grade, which reflect the extent of disease and its biological aggressiveness, respectively.

Histological evaluation is frequently complemented by immunohistochemical analysis, which is used both for diagnostic characterization of the lesion and for predicting response to specific systemic therapies. In particular, assessment of PD-L1 expression is considered essential in the evaluation of lung cancer.

PD-L1 testing helps determine whether a patient may benefit from immunotherapy, a treatment strategy designed to enhance the immune system’s ability to recognize and attack tumor cells. Results are generally reported as a percentage of tumor cells expressing PD-L1 and may significantly influence therapeutic decision-making.

Comprehensive histological and immunohistochemical evaluation requires a variable amount of time depending on the complexity of the case; in most cases, final reporting by the anatomic pathologist requires at least seven working days.

This approach involves DNA and RNA extraction from tissue samples (as obtained through histological examination) or from liquid biopsy (peripheral blood sampling), followed by somatic genomic profiling to identify clinically relevant genetic alterations, including mutations, gene fusions, and copy number variations (amplifications).

The technique employed is Next-generation sequencing (NGS) using targeted gene panels that enable simultaneous analysis of hundreds of genes (up to approximately 517), thereby providing a comprehensive overview of the tumor’s molecular landscape.

Detection of these molecular alterations is essential for identifying eligibility for molecularly targeted therapies (also known as precision oncology or targeted therapy), which are designed to produce rapid and durable responses and are often associated with a more favorable toxicity profile compared with conventional chemotherapy.

This analysis is technically complex and is typically performed immediately after histological confirmation of malignancy. Reporting generally requires approximately 10–15 working days to complete.

Surgery, when feasible, is the preferred treatment for resectable, nonmetastatic non-small-cell lung cancer (NSCLC).

Depending on the histologic and molecular characteristics of the tumor, as well as the definitive disease stage, surgery may be preceded or followed by chemotherapy, immunotherapy, radiotherapy, or other systemic antineoplastic treatments.

Surgical management of lung cancer includes a range of lung resection procedures performed through either open surgery or minimally invasive techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic-assisted surgery.

Lung resections are classified according to the amount of lung tissue removed:

• Wedge resection: removal of a small, wedge-shaped portion of lung tissue containing the tumor
• Segmentectomy (segmental resection): removal of one or more bronchopulmonary segments, which are subdivisions of a lobe
• Lobectomy: removal of an entire lung lobe. The right lung consists of three lobes, whereas the left lung has two
• Pneumonectomy: removal of an entire lung

Surgical treatment for lung cancer is typically accompanied by resection of regional lymph nodes, including hilar and mediastinal nodes, for accurate staging and local disease control.

The choice of surgical procedure and operative approach depends on several factors, including tumor stage, anatomical location, the patient’s overall clinical condition, and pulmonary functional reserve.

In small-cell lung cancer (SCLC), surgery is rarely part of standard treatment because the disease has often metastasized by the time of diagnosis.

Radiation therapy for lung cancer is a localized, noninvasive treatment, typically administered on an outpatient basis, that destroys tumor cells using high-energy ionizing radiation.

Treatment is delivered using specialized equipment, such as linear accelerators and tomotherapy systems. Radiotherapy may be used for early-stage disease, local recurrence (either as an alternative to surgery or as adjuvant treatment after surgery), in combination with chemotherapy for locally advanced tumors, or as palliative therapy to relieve symptoms caused by the primary tumor or metastatic disease.

A specialized form of treatment available at our institute is stereotactic body radiotherapy (SBRT) for primary or metastatic lung lesions. SBRT enables the delivery of highly precise, high-dose radiation to small lung lesions over a limited number of treatment sessions, minimizing exposure to surrounding healthy tissues. Treatment planning also accounts for respiratory motion to ensure accurate targeting despite lung movement during breathing.

Radiation therapy is generally well tolerated; however, both acute and late adverse effects may occur. Acute toxicities may include cough, dyspnea, fatigue, skin irritation or burning, and swallowing difficulties (dysphagia). Late toxicities can include radiation pneumonitis or pulmonary fibrosis. The incidence and severity of these effects depend on the radiation dose and treatment volume and may be exacerbated by smoking.

Chemotherapy for lung cancer is a systemic medical treatment that uses cytotoxic drugs to destroy cancer cells and inhibit their growth and spread throughout the body. Chemotherapy may be administered intravenously or orally, typically in cycles alternating with recovery periods. It can be used before surgery (neoadjuvant therapy), after surgery (adjuvant therapy), or for symptom control and disease management in advanced-stage cancer.

Chemotherapeutic agents may be administered either in combination regimens or as single agents. The selection of drugs, particularly in advanced disease, depends on the histologic subtype and molecular characteristics of the tumor; therefore, accurate pathological diagnosis is essential. Chemotherapy is now frequently combined with targeted therapies or immunotherapy to improve treatment efficacy.

The adverse effects of chemotherapy vary according to the specific drugs used, but common side effects include nausea and vomiting, fatigue (asthenia), temporary reductions in blood cell counts (including red blood cells, white blood cells, and platelets), hair loss, oral mucositis or ulcers, diarrhea or constipation, and peripheral neuropathy characterized by numbness or tingling in the extremities.

Additional side effects may include immunosuppression, fever, and skin reactions. Patients should promptly report any symptoms to their oncology team, as supportive treatments are available, including antiemetics for nausea, medications for neuropathy management, growth-factor support, and blood transfusions when necessary.

Precision medicine (targeted therapy) for lung cancer uses drugs designed to inhibit specific molecular alteration, most commonly genetic mutations, present in tumor cells. By targeting pathways involved in cancer cell growth and survival, these therapies act more selectively than conventional chemotherapy.

To determine whether a patient with non-small-cell lung cancer (NSCLC) is eligible for targeted therapy, comprehensive molecular profiling of the tumor tissue obtained through biopsy is required, typically using next-generation sequencing (NGS).

Several actionable molecular alterations can now be treated with approved targeted agents or investigational therapies, including alterations involving EGFR, ALK, ROS1, BRAF, NTRK, RET, KRAS, MET exon 14 skipping, and HER2.

Targeted therapies are commonly administered orally in tablet form or by intravenous infusion and may be used alone or in combination with chemotherapy, immunotherapy, or other treatments.

Because these drugs specifically target molecular abnormalities in cancer cells, they may spare healthy tissues to a greater extent than traditional chemotherapy, potentially resulting in a more favorable side-effect profile. Nevertheless, adverse effects can still occur and vary according to the specific agent used. Common side effects include skin reactions (such as rash and dryness), gastrointestinal disturbances (particularly diarrhea), and fatigue. Other possible toxicities include hypertension, cardiac complications, thyroid dysfunction, and, in some cases, interstitial lung disease or pneumonitis.

Patients should promptly report any symptoms to their oncologist so that appropriate supportive care and toxicity management can be initiated.

In recent years, immunotherapy has revolutionized the treatment of lung cancer. Unlike conventional therapies that directly target tumor cells, immunotherapy uses drugs that stimulate the patient’s immune system to recognize and destroy cancer cells. This is primarily achieved by blocking immune checkpoint pathways, molecular “brakes” that tumor cells exploit to evade immune surveillance, thereby restoring the ability of T lymphocytes to mount an effective antitumor response.

In non-small-cell lung cancer (NSCLC), immunotherapy is used across multiple stages of disease. It may be administered in combination with chemotherapy before surgery (neoadjuvant therapy), after surgery as adjuvant treatment to reduce the risk of recurrence, after chemoradiotherapy in locally advanced disease, or in metastatic disease either alone or combined with chemotherapy to enhance treatment efficacy.

A key predictive biomarker for immunotherapy response is the expression of programmed death-ligand 1 (PD-L1) on tumor cells. PD-L1 testing plays an important role in determining eligibility for and selection of immunotherapeutic strategies.

In advanced-stage small-cell lung cancer (SCLC), the combination of chemotherapy and immunotherapy is currently considered the standard first-line treatment.

The adverse effects of immunotherapy differ from those of chemotherapy and are mainly related to excessive activation of the immune system, which may also affect healthy tissues. Common side effects include endocrine disorders such as hypothyroidism, skin reactions (rash, pruritus, dryness), gastrointestinal symptoms (diarrhea and abdominal pain), fatigue, musculoskeletal pain, and flu-like symptoms including fever and chills.

Less frequent but potentially serious immune-related adverse events include hypophysitis and other endocrine toxicities, pneumonitis, and hepatitis, all of which require prompt recognition and careful medical management.

Patients should report any new or worsening symptoms promptly to their oncology team so that appropriate supportive care and treatment can be initiated.

The management of oncologic emergencies related to lung cancer requires a multidisciplinary approach involving pulmonologists, thoracic surgeons, medical oncologists, radiation oncologists, dietitians, palliative care specialists, psychologists, nurses, and other healthcare professionals to ensure timely and effective patient care.

All of these specialists are represented within the institute and can be contacted during regular business days and hours through the dedicated oncology service telephone numbers or via the secretary of the Interdisciplinary Lung Cancer Care Group at +39 011 9933069.

In the event of urgent, non-deferrable medical conditions, or during nighttime, weekends, or holidays, patients should be referred promptly to the emergency department of the nearest appropriate hospital.

Maintenance therapy in lung cancer refers to treatment administered after completion of first-line therapy, such as chemotherapy or chemoradiotherapy, with the aim of maintaining disease control and delaying tumor progression. Maintenance treatment may involve continuation of one of the agents used during first-line therapy or the introduction of other treatments, including immunotherapy, targeted therapies, or maintenance chemotherapy, depending on the histologic subtype, molecular profile, prior treatments, and stage of disease.

Palliative care services are also available at the institute to support symptom management, improve quality of life, and address the physical, psychological, and supportive needs of patients throughout the course of their disease.

The impact of cancer on a person’s life also extends to the psychological domain. A cancer diagnosis is often a traumatic event that affects all dimensions of the individual and may generate anxiety, fear, anger, and depression.

At the Candiolo Cancer Institute, alongside advanced medical treatments, the care pathway includes qualified psycho-oncological support to help patients cope constructively not only with treatment but also with the delicate phase of physical and psychological recovery.

Patients may also participate in psychological support groups, allowing them to share experiences and connect with others who have faced or are currently facing a similar journey.

The Social Service of the Candiolo Institute provides informational and orientation interviews for patients and their families on how to access local services and how to obtain legally provided welfare and social security benefits, including disability support, assistance for aids and prostheses, and work leave provisions.

The service is available on Wednesdays and Fridays from 9:00 a.m. to 1:00 p.m. and can be contacted at +39 011 9933059.

Follow-up of lung cancer refers to the post-treatment surveillance phase, which includes periodic clinical evaluations and diagnostic tests, such as CT scans with or without contrast and blood tests, to detect possible disease recurrence or the development of a second primary tumor.

The frequency and duration of follow-up visits, typically starting with closer intervals (every 4–6 months) and gradually becoming less frequent over time, depend on the stage of the disease and individual patient characteristics, and are established in agreement with the treating specialist.

Due to the high volume of cases treated each year, the Candiolo Cancer Institute is a national reference center for the management of pancreatic cancer. Our experience enables us to address even the most complex clinical situations, consistently adopting a personalized approach tailored to the clinical and individual profile of each patient.

The definition of the treatment plan always begins with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies that enable precise assessment of disease extent.
In addition, the Institute provides advanced laboratory investigations, including molecular and genomic analyses, which are essential for identifying the biological characteristics of the tumor and guiding therapeutic decision-making.

When indicated, surgery is performed with minimally invasive techniques (laparoscopic or thoracoscopic), which reduce operative trauma, facilitate faster recovery, and improve postoperative quality of life. Every treatment choice is defined within the GIC – the Multy Disciplinary Team, ensuring a consistent and integrated approach.

As an IRCCS, the Candiolo Cancer Institute integrates clinical practice with a strong commitment for scientific research. Patients may be assessed for inclusion in active clinical trials,

The GIC, Interdisciplinary Care Group, or Multidisciplinary Team, supports the patient at every stage of the care pathway, from diagnosis to treatment and follow-up, with particular attention to nutritional support, psychological well-being, and reintegration into daily life. The organization of check-ups, consultations, and treatments is designed to ensure continuity of care and peace of mind, always placing the human dimension of care at the center.