The role of surgery in the management of lung cancer consists of performing a biopsy for diagnosis and biomarker-NGS testing to identify cancer causing mutations that can be treated with precision cancer medicines or immunotherapy, determining the correct stage of the cancer in order to ensure optimal treatment and treating the cancer by surgical removal in selected situations. The decision to treat lung cancer surgically depends on the type of lung cancer, as well as several prognostic factors. Surgery is a common form of treatment for non-small cell lung cancer (NSCLC), whereas, it is not as commonly used with small cell lung cancer.
Historically lung cancer was diagnosed and treated by a thoracic surgeon. More recently clinical studies have convincingly demonstrated that precision cancer medicines and immunotherapy administered before or after surgery significantly improve survival rates for lung cancer. Management of lung cancer by surgeons alone has been replaced by a multi-disciplinary team consisting of pulmonologists, medical oncologists, surgeons, and radiation oncologists working together.1,2,3
Role of Surgery in Lung Cancer
- Obtaining a biopsy to make a correct diagnosis.
- Primary treatment of the cancer itself through surgical removal.
- Obtaining tissue to identify cancer growth driving mutations that can be treated with precision cancer medicines
- Determining the correct stage of the cancer in order to ensure optimal treatment.
Biopsy Diagnosis of Lung Cancer
Following the identification of an area suspicious for cancer on x-ray or PET/CT scan a tissue biopsy is required to determine if cancer is present. During a biopsy, small pieces of suspicious tissue or fluids are removed from the body and examined under a microscope by a doctor called a pathologist. When discussing a biopsy with their doctor patients should make sure tissue is being send to test for PD-L1, and ctDNA evaluation for cancer causing mutations. The results of these tests are essential for optimal treatment of the cancer. Depending on the location of the suspected cancer tissue can be obtained by one of the following procedures or by surgical removal of the suspected cancer itself.
- CT Guided Fine Needle Aspiration Biopsy: CT guided fine needle aspiration biopsy is the most common way to evaluate possible cancers. A CT scan takes a very detailed picture of a patient’s suspected cancer, allowing the insertion of a thin needle to remove a sample of the tissue. This gives doctors the most information without resorting to a more invasive surgery (thoracotomy) and direct biopsy.
- Bronchoscopy - A thin, flexible tube (bronchoscope) is inserted into the lungs through the nose or mouth. A small camera is used to look directly into the lungs, and a needle can be inserted into the bronchoscope to take tissue samples. Bronchoscopy is typically performed by a lung specialist called a pulmonologist.
- Transbronchial Needle Aspiration (TBNA) is a procedure to obtain cellular material using a needle that is passed through the bronchial wall. It is used to obtain tissue from lung or hilar/mediastinal lesions that are in close proximity to the endobronchial tree.
- Autofluorescence Bronchoscopy. A bronchoscope is inserted into the lungs through the nose or mouth. A special light is used with a camera, which captures live color video which is viewed on a monitor. Under this light, abnormal/pre-cancerous tissue appears in a different color than normal tissue.
- Endobronchial Ultrasound (EBUS) - A type of ultrasound combined with a bronchoscope is inserted through the mouth. A tissue biopsy can be performed and EUS allows for optimal examination of the lymph nodes and other structures in the center of the chest to see if cancer has spread. This technique is performed in order to avoid the more invasive procedures of mediastinoscopy or thoracotomy. EBUS-FNA is more sensitive for detecting the cancer cells than Transbronchial Needle Aspiration (TBNA), detecting 69% of malignant lymph nodes, compared to 36% for TBNA in one study. In combination, EUS-FNA and EBUS-FNA had an even greater sensitivity rate of 93%, which was better than either method used alone.18-20
- Mediastinoscopy - A surgical procedure in which an incision made just above the breastbone allows a device with a camera attached to pass into the middle of the chest to see if cancer is present there and to check central lymph nodes for cancer.
- Thoracentesis. A hollow needle is used to draw fluid that has collected between the lungs and the chest wall.
- Thoracoscopy. A surgical procedure in which an incision in the chest wall allows a device with a camera attached to be inserted into the lungs so the lungs and surrounding area can be explored.
- Thoracotomy: During a thoracotomy, a surgeon makes a large incision in a patient’s chest in order to directly access the mass and directly remove part or all of the suspicious area. In some patients with a peripheral lung mass and no evidence of mediastinal or systemic cancer, a wedge resection of the lesion is sometimes performed and diagnosis made on a frozen-section of tissue. If lung cancer is confirmed, a formal cancer resection is then performed.
Surgical Treatment of NSCLC
There are two main types of lung cancer; non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), which together account for over 90% of all lung cancers.
Small cell lung cancer is not typically treated with surgery because the disease is usually widespread at the time of diagnosis. Once a diagnosis of SCLC is made and the amount of disease is characterized as either limited or extensive, patients typically receive treatment with systemic therapy and possibly radiotherapy. However, good results from surgery alone have been reported in a small subgroup of patients that have a small primary cancer and no lymph node involvement. Sometimes surgery is used in conjunction with chemotherapy and/or radiation therapy, but the contribution of surgery to overall outcome is not clear in this setting.1,2,3
Approximately 45% of all patients with NSCLC will have cancer that is limited to the chest. For these patients, surgical resection is not only an important therapeutic modality, but in many cases, the most effective method of controlling the disease. Patients with stages I-II localized NSCLC without spread to lymph nodes are considered to have early-stage disease and should have their cancer removed by surgery if possible.1-3 Systemic treatment with precision cancer medicines and immunotherapy based on NGS-biomarker testing following surgery further improves survival. Surgery can be safely performed before or after systemic treatment and patients should discuss the optimal timing of surgery with their doctor. Patients with stage III NSCLC may be treated with either neoadjuvant systemic therapy based on NGS-biomarker testing followed by surgery or combined treatment with systemic therapy and radiation therapy after surgery.4-7,17
NSCLC Outcomes with Surgery Alone
Surgery alone can be used to treat early stage NSCLC but when surgery is combined with chemo-immunotherapy long term survival rates are improved by ~10%.
Five year survival rates for NSCLC patients treated with surgery alone have been reported.8
- Stage I and II NSCLC is 58% and 28.%.
- Stage IIIA disease had a survival rate of 15.1%.
- Stage IIIB is 24.1%.
- Stage IV is 21.1%.
Older patients are more likely than younger patients to have health problems that prevent them from having surgery. However, elderly patients, over 75-80 years of age who are in good physical condition do as well after surgery as younger patients. Decisions about surgery should not be based on age alone.15,16
Treatment of Stage I - IIIA Non-Small Cell Lung Cancer
Update on the management of early stage NSCLC: three trials confirm benefit of immunotherapy yet many patients still not receiving treatment.
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Types of Lung Cancer Surgery
The surgical procedure to remove a lung cancer is called a thoracotomy. During a thoracotomy the surgeon may remove part or all of a lung. A “wedge resection removes” a very small part of the lung and a “segmentectomy” removes a slightly larger part of lung based on anatomical segments. These types of operation are used when the cancer has been diagnosed early and is only in one very small area. A lobectomy is the removal of one lobe of the lung and is the most frequent operation performed for early-stage NSCLC. A pneumonectomy is the removal of the entire lung. This procedure is performed when the cancer is found to involve more than one lobe. Pneumonectomy is associated with more than twice the mortality rate of lobectomy, as well as more long-term pulmonary side effects. Historically all lung cancer surgeries were performed with an open thoracotomy however major cancer centers are increasingly using minimally invasive surgical techniques to improve outcomes.
Research suggests that a lobectomy, particularly for cancers less than 3 centimeters, appears to improve outcomes compared with wedge resections for patients with stage IA NSCLC.13
Segmentectomy for Stage I NSCLC
In the open-label multi-center trial, 1,106 patients with clinical stage IA disease (tumor diameter ≤ 2 cm; consolidation-to-tumor ratio > 0.5) were randomly treated with segmentectomy or lobectomy. Adjuvant therapy was received by 47 patients in the segmentectomy group. At a median follow-up of 7.3 years (he 5-year overall survival was 94.3% compared with 91.1% in the segmentectomy group. The findings suggest that segmentectomy should be the standard surgical procedure.21
Minimally invasive surgery reduces lung tissue damage, is associated with a shorter period of impaired immune function and achieves overall higher compliance rates and fewer delayed or reduced doses of post-operative systemic adjuvant therapy. Video-Assisted Thoracoscopic Surgery or “VATS” is gradually replacing the conventional open thoracotomy in appropriate patients. Patients are encouraged to speak to their physician regarding surgical options and individual risks and benefits of specific surgical procedures.9-12
Minimally Invasive Surgery: Robotics and Video-Assisted Thoracoscopic Surgery (VATS) for Early Stage Cancer:
Minimally invasive robot-assisted lung surgery may provide better quality of life compared with video-assisted lung surgery, according to research released at the IASLC 2022 World Conference on Lung Cancer in Vienna.23
Video-Assisted Thoracoscopic Surgery (VATS) is a form of minimally invasive surgery that utilizes a television camera and has widely replaced open thoracotomy in the management of earlier stage lung cancers. During a VATS procedure, a tiny camera (thoracoscope) and surgical instruments are inserted into the chest through one or more small incisions in the chest wall. The thoracoscope transmits images of the inside of the chest onto a video monitor to guide the surgeon in performing the procedure. The advantages of the camera-aided procedures are that smaller incisions can be used and there is no need to cut through a rib, which is necessary for conventional thoracotomy. This results in quicker, less intrusive surgery, with a much smaller scar.
Robotic surgery is a surgical procedure performed in a minimally invasive fashion and also involves using enhanced imagery. Compared to VATS, robotic surgery allows surgeons to more precisely control the surgical instruments because they offer seven degrees of free motion (like a wrist).
Using these new procedures requires significant skill and a great deal of training. There is less, or at least different, visibility and if a serious problem arises minimally invasive procedures can be converted to an open or traditional procedure, creating a small additional risk.9 Clinical studies have demonstrated similar effectiveness between a thoracotomy and a VATS procedure for the surgery of lung cancer, with reduced side effects with VATS.9,10
Researchers from four academic sites in the United States, Canada and France compared the outcomes of 406 patients with early-stage lung cancer treated with minimally invasive robotic lobectomy or traditional VATS-Lobectomy. Researchers found that patients undergoing robotic surgery had improved quality of life and significantly more lymph nodes were sampled which is critical for effective staging. Robotic surgery was also more cost effective.
A thoracotomy is a surgical procedure to open the chest and remove cancerous lung tissue. This surgical procedure is performed under general anesthesia. In order to reach the affected lung lobe, surgeons performing a thoracotomy have to break some of the patient’s ribs and create a long incision through large muscle layers on the patient’s side and back. Following surgery, patients undergoing a thoracotomy must be closely monitored in the hospital for approximately 2 weeks. Chest tubes (tubes placed in the chest which allow excess drainage to be collected outside the body) are needed temporarily and severe long-term pain is often a side effect from the surgery. These problems have led surgeons to develop less invasive surgical techniques to perform a lobectomy.
Post Treatment Surveillance Detects Surgically Treatable Second Cancers.
Close follow-up screening may detect early second cancers in patients already considered cured following the surgical removal of early-stage NSCLC. Researchers from the City of Hope National Medical Center conducted a clinical study to evaluate the effectiveness of close follow-up in 124 patients with stage IA NSCLC previously treated with surgery alone. Follow-up included an annual computed tomographic (CT) scan of the chest with interval chest x-rays every 4 months for 2 years and every 6 months for 3 additional years. During this time, 14 patients were found to have developed a second NSCLC and received further surgery. Patients with previously treated stage early stage NSCLC should participate in an active surveillance program following treatment.14
- American Cancer Society. Cancer Facts & Figures 2017.
- Tagrisso – First Precision Medicine Approved for Treatment of Early Stage NSCLC
- Opdivo (nivolumab) Plus Chemotherapy Shows Statistically Significant Improvement in Pathologic Complete Response as Neoadjuvant Treatment of Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate-816 Trial [news release]. Princeton, NJ. Published October 7, 2020. Accessed October 7, 2020.
- FDA approves atezolizumab as adjuvant treatment for non-small cell lung cancer. News release. October 15, 2021. Accessed October 15, 2021. https://bit.ly/3lHUgv
- Wakelee HA, Altorki NK, Zhou C, et al. IMpower010: primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC). J Clin Oncol. 2021;39(suppl 15):8500. doi:10.1200/JCO.2021.39.15_suppl.8500.
- Strand T-E, Rostad H, Moller B, Norstein J. Survival After Resection of Primary Lung Cancer: a Population Based Study of 3211 Resected Patients. Thorax. 2006; 61:710-715.
- Roviaro G, Varoli F, Vergani C, et al. Long-term survival after videothorascopic lobectomy for stage I lung cancer. Chest . 2004; 126: 725-732.
- Luketich J, Meehan M, Landreneau R, et al. Total videothroacoscopic lobectomy versus open thoracotomy for early-stage non small-cell lung cancer. Clinical Lung Cancer. 2000;2:56-60.
- Clinical Lung Cancer, Vol 2, No 1, pp 56-60, 2000
- Petersen R, DuhKhanh P, Burfeind W, et al. Thoracoscopic Lobectomy Facilitates the Delivery of Chemotherapy after Resection for Lung Cancer. Annals of Thoracic Surgery. 2007; 83:1245-1250.
- Kraev A Rassias D, Vetto J, et al. Wedge resection vs lobectomy. Chest. 2007; 131:136-140.
- Lamong J, Kakuda J, Smith D, et al. Systematic postoperative radiologic follow-up in patients with non-small cell lung cancer for detecting second primary lung cancer in stage IA. Archives of Surgery. 2002;137:935-939.
- Sawada S, Komori E, Nogami N et al. Advanced age is not correlated with either short-term or long-term postoperative results in lung cancer patients in good clinical condition. Chest. 2005;128:1557-1563.
- Dillman R, et al. Proceedings from the American Association for Cancer Research 2008 Annual Meeting: Abstract 5537. Presented April 16, 2008.
- Cerfolio R, Bryant A, Spencer S, Bartolucci A. Pulmonary Resection after High-Dose and Low-Dose Chest Irradiation. Annals of Thoracic Surgery. 2005; 80:1224-1230.
Wallace, M, Pascual, J, Raimondo, M, et al. Minimally invasive endoscopic staging of suspected lung cancer. Journal of American Medical Association. 2008. 299(5) 540-546
Lloyd C, Silvestri GA. Mediastinal Staging of Non-small Cell Lung Cancer. Cancer Control. 2001;8:311-317.
Herth FJF, Eberhardt R, Vilmann P, Krasnik M, Ernst A. Real-time Endobronchial Ultrasound Guided Transbronchial Needle Aspiration for Sampling Mediastinal Lymph Nodes. Thorax. 2006;61:795-798.