Treatment of NSCLC (Non Small Cell Lung Cancer) according to Stage
The treatment of NSCLC mainly depends on the stage, type, location of the tumor, pulmonary function, performance status of the patient, presence of certain genetic abnormalities, along with other factors.
Following is the preferred treatment approach for different stages of NSCLC, but the final decision is taken after clinical assessment of the patient by an oncologist.
Stage 0 (Tis N0 M0)
Stage 0 NSCLC is limited to the superficial layer of the airway and can be treated by surgery alone as the standard treatment. Sometimes, endobronchial therapies like photodynamic therapy (PDT), laser therapy, or brachytherapy may be employed to treat Stage 0 NSCLC.
Surgery resection with mediastinal lymph node dissection is the standard treatment. Chemotherapy may be added in selected cases. In inoperable cases (poor lung reserve, poor performance status, etc), radiation therapy may be employed as the primary treatment.
Surgical resection with mediastinal lymph node dissection is done, while preoperative chemoradiation may be considered in selected cases. Chemotherapy should be considered after surgery. In inoperable cases, chemotherapy and/or radiotherapy may be given.
Stage III NSCLC treatment generally includes a combination of surgery, radiation therapy, and chemotherapy. The overall treatment approach depends on the size and location of the tumor, the location of the lymph node involved, and overall health status of the patient.
Stage IV (Metastatic disease)
Chemotherapy, targeted therapy or immunotherapy is the mainstay of treatment. Other treatment options like surgery, radiation therapy or bone-directed therapy may be considered for palliation or relief of symptoms.
This brings us to the end of treatment for lung cancer. Now let’s discuss the various treatment modalities for lung cancer in detail.
Surgery for Lung Cancer
Surgery is the treatment of choice for early stage and some advanced stage lung cancers that have not spread to distant body parts and can be completely removed. For early-stage disease, a tumor can be removed with segmentectomy, wedge resection, or sleeve resection, where only a part of the affected lobe is removed.
In case of advanced stage disease, lobectomy (surgical removal of the entire globe) or pneumonectomy (surgical resection of the entire lung) may be required depending on the size and location of the tumor. Surgery can also be employed as a palliative treatment for an advanced-stage disease to relieve airway obstruction by a growing tumor.
Targeted Therapy for Lung Cancer
What is targeted therapy for lung cancer?
- Lung cancer is a heterogeneous disease, that is, all individuals with the same cancer type do not contain the same mutations/alterations.
- Targeted anticancer therapy means treatment with specially designed drugs that produce their anticancer effect by selectively modifying a target (key to the growth of cancer cells).
- Examples of such targets include genetic or epigenetic alterations, chromosome/genetic rearrangements, cell-surface proteins/antigens, or certain molecular pathways in the cancer cells that promote growth and are responsible for disease progression.
- Targeted therapy helps in the selective destruction of cancer cells while sparing normal cells, which leads to a decrease in the overall side effects compared to standard chemotherapeutic drugs.
What Targeted therapies are available for the treatment of lung cancer?
Lung cancer is the leading causes of cancer-related deaths worldwide and is assessed to be the second most frequently diagnosed cancer in men and women. The following table list various targeted drug that has been approved for the treatment of NSCLC:
It is approved for the treatment of patients with unresectable, locally advanced, recurrent, or metastatic non-squamous NSCLC and without a recent history of hemoptysis. It can also be given along with chemotherapy for the treatment of patients with non-squamous NSCLC, and negative or unknown status of ALK/ROS1 rearrangements, sensitizing EGFR mutations, and PD-L1 expression <50%.
In combination with chemotherapy, it is approved for the treatment of patients with metastatic NSCLC whose disease has progressed on or after first-line platinum-based chemotherapy.
Gefitinib and Erlotinib
Both Gefitinib and erlotinib are approved as first-line therapy for patients with locally advanced, recurrent, or metastatic non-squamous NSCLC who have active sensitizing EGFR mutations.
It is an EGFR and HER2 inhibitor approved as the first-line therapy for patients with metastatic NSCLC who have active sensitizing EGFR mutations.
It is an EGFR and T790M inhibitor approved as the first-line therapy for patients with locally advanced or metastatic NSCLC who have sensitizing EGFR mutations. It is also approved as the subsequent therapy for patients with metastatic EGFR and T790M-positive NSCLC who have progressed on erlotinib, gefitinib, or afatinib.
It is an ALK and ROS1 inhibitor approved for the treatment of patients with locally advanced, metastatic, ALK and/or ROS1 rearrangement-positive NSCLC.
It is an ALK and ROS1 inhibitor approved for the treatment of patients with locally advanced, metastatic, ALK and/or ROS1 rearrangement-positive NSCLC who cannot tolerate crizotinib or have progressed on crizotinib treatment.
It is an ALK and MET inhibitor approved for the treatment of patients with locally advanced, metastatic, ALK rearrangement-positive NSCLC. It is also approved for the treatment of patients with metastatic, ALK-positive NSCLC who cannot tolerate crizotinib or have progressed on crizotinib treatment.
It is an ALK inhibitor approved for the treatment of patients with metastatic, ALK-positive NSCLC who cannot tolerate crizotinib or have progressed on crizotinib treatment.
Dabrafenib + trametinib combination is approved for the treatment of patients with metastatic, BRAF V600E positive NSCLC. Single-agent therapy with dabrafenib can also be given to patients with metastatic, BRAF V600E positive NSCLC who cannot tolerate the combination therapy.
Immunotherapy for Lung Cancer
As described above, there are many different types of immunotherapeutic agents. These are used for advanced-stage NSCLC without epidermal growth factor receptor (EGFR) activating mutation, anaplastic lymphoma kinase (ALK) rearrangement, or ROS1 rearrangement. Following immunotherapeutic agents are approved for the treatment of advanced-stage non-small cell lung cancer (NSCLC):
First-line treatment of patients with and who express >/=50% PD-L1. For patients with PD-L1 expression <50% but >1%, it can be combined with chemotherapy for the first-line treatment. Subsequent treatment of patients with metastatic non-squamous or squamous NSCLC and PD-L1 expression levels of >/=1%.
Treatment of patients with advanced-stage metastatic squamous NSCLC and non-squamous NSCLC who have experienced disease progression on or after standard platinum-based chemotherapy (regardless of tumor PD-L1 protein expression).
Combined with chemotherapy with/without targeted therapy, atezolizumab can be given as first-line treatment of patients with metastatic non-squamous NSCLC. Subsequent treatment for patients with metastatic non-squamous or squamous NSCLC and PD-L1 expression levels of >/=1%.
It is recommended as consolidation treatment for patients who have not progressed after concurrent chemoradiation treatment for unresectable stage III NSCLC.
What are the advantages of Immunotherapy for Lung cancer Treatment?
- It is the preferred treatment for the second-line treatment of advanced-stage NSCLC due to improved overall survival rate, longer duration of response, and fewer side-effects compared to standard chemotherapy.
- It can be combined with chemotherapy and targeted therapy for first-line treatment of advanced-stage disease with a better outcome.
What are the disadvantages of Immunotherapy for Lung cancer Treatment?
- Although the immunotherapy is considered safer compared to the standard chemotherapy, it can be associated with certain side-effects.
- Side effects of immunotherapy include fatigue, nausea, itching, skin rash, mouth sores, cough, high blood pressure, fluid build-up in legs, constipation, loss of appetite, joint pain, diarrhea, etc.
- Other less common severe side-effects include immunological reactions such as pneumonitis have also been reported.
- Also, it takes more time to act as compared to other treatment modalities, so it is not a preferred option for patients who require a high reponse rate for symptomatic disease.
Chemotherapy for Lung Cancer
It may be used in the neoadjuvant (prior to surgery), adjuvant (after surgery) and palliative (metastatic disease) settings.
Some chemotherapy drugs that are a part of treatment regimens for lung cancer are-
Radiation Therapy for Lung Cancer
Radiation therapy (or radiotherapy) uses high-energy radiation directed to the affected area to kill cancerous cells. It can be employed either by using an external radiation source (external beam radiation therapy) or by directly placing the source of radiation near the cancer tissue (brachytherapy). Sometimes, it is used as palliative therapy to relieve pain, bleeding, and obstructive problems associated with the advanced-stage disease.
Treatment of SCLC (Small Cell Lung Cancer)
Similar to NSCLC, the treatment for SCLC depends on the stage assigned to the disease with the help of the investigational tests. Very few patients are diagnosed with Stage I SCLC who can be considered the candidates for surgical resection. Thus, chemotherapy with or without radiotherapy remains the mainstay of the treatment.
Preferred treatment approaches for different stages of SCLC:
Chemotherapy with or without radiotherapy is the preferred treatment for the limited-stage SCLC. Surgery may be employed for an early-stage disease, but chemotherapy with or without radiotherapy is generally recommended after surgery due to a high recurrence rate of SCLC. Prophylactic cranial irradiation may also be employed to prevent the spread of disease to the brain as per physician’s discretion.
Chemotherapy with or without radiotherapy is the preferred treatment for the extensive-stage SCLC. Radiation therapy is usually employed for the disease spread to distant organs not directly benefitted from chemotherapy. Prophylactic cranial irradiation may also be employed to prevent the spread of disease to the brain as per physician’s discretion.