Lung Cancer Treatment: Surgery

Kavish Khatib

1. Aetiology

2. Classification

3. Staging

4. Signs and symptoms

5. Diagnosis

6. Surgical treatment

1. SCLC

2. NSCLC

7. Types of surgery

8. Survival

Lung carcinoma

• Lung tumours may be primary or metastatic from other sites of the body. They may be malignant or benign

• The most common lung tumour is lung carcinoma also known as bronchogenic carcinoma or lung cancer.

• Lung carcinoma is the leading cause of cancer-related death worldwide.

Aetiology 1. Cigarette smoking is the most important cause of lung cancer - 85%

• The risk differs by age, intensity of smoking and duration • The risk of cancer declines after smoking cessation.

2. 15% of patients have never smoked.• Radon exposure• Occupational factors: asbestos, radiation, arsenic, nickel , mustard gases • Genetic mutations in the epidermal growth factor Gene (EGFR)

3. Risk increases with combination of exposure to occupational carcinogen, toxins and cigarette smoking

4. People whose lungs are scarred by other lung diseases have an increased risk of of lung carcinoma

• TB, COPD & Pulmonary fibrosis (alpha1 anti-trypsin deficiency)

5. Respiratory epithelial cells require prolonged exposure to cancer-promoting agents and accumulation of multiple genetic mutations before becoming neoplastic which is carcinogenesis. Over time, mutations in genes stimulate cell growth factor receptor signalling (EGFR, HER2/neu)m inhibit apoptosis (BCL-2) and contribute to the proliferation of abnormal cells. In addition, mutations that inhibit tumour-suppressor genes (P53, APC) can lead to cancer

Classification

1. 2 major classifications

• Small lung carcinoma (SCLC) previous name Oat cell carcinoma - 13-15%

• Non-small cell carcinoma (NSCLC) - 85%

2. SCLC - Highly aggressive and almost always in smokers. Not usually amenable to surgical resection

Staging of system of Lung cancer

Signs and symptoms 1. Proximal tumours tend to produce symptoms of major

airway obstruction and irritation, stridor, hoarseness, SVC

2. Peripheral tumours are often asymptomatic or present with signs and symptoms of pleural or chest wall invasion or pleural effusion

3. Metastatic spread: Symptoms vary by location

1. Neurological: headache, blurred vision, nausea, diplopia

2. Bone metastasis: sever pain and pathological features

3. Adrenal glands:

4. Para-neoplastic syndromes

Diagnosis

• Chest X-ray

• CT

• Cyto-pathology of pleural or septum

• Bronchoscopy

• Screening

Surgical treatment 1. Surgery (depending on cell type and stage)

2. Chemotherapy

3. Radiation therapy

• Treatment varies by cell type and by stage of disease. • Poor cardiopulmonary reserve, undernutrition, • frailty or poor physical performance status (assessed by, eg, Karnofsky

performance status [KPS] or Eastern Cooperative Oncology Group performance status [ECOGPS]),

• Radiation therapy carries the risk of radiation pneumonitis when large areas of the lung are exposed to high doses of radiation over time. Cough, dyspnea, low-grade fever, or pleuritic chest pain may signal the condition, as may crackles or a pleural friction rub detected on chest auscultation.

• Radiofrequency ablation, in which high-frequency electrical current is used to destroy tumor cells.This procedure may preserve more lung function than open surgery does

SCLC• Historically, patients undergoing surgery for small cell lung cancer (SCLC)

had a dismal prognosis.

• Surgery was abandoned for SCLC almost 30 years ago after the results of the Medical Research Council randomized trial revealed a significant survival difference between surgery and radiotherapy, a 4-year survival of 3% and 7%, respectively, and a 5-year survival of 5% in the radiotherapy arm.

• However, more recent data suggest that patients with true stage I SCLC may benefit from surgical resection.

• The American College of Chest physicians (ACCP) recommends that patients being considered for resection undergo invasive mediastinal staging and extrathoracic imaging, such as cranial computed tomography (CT) scanning or magnetic resonance imaging (MRI), abdominal CT scanning, and bone scanning

NSCLC1. Treatment for NSCLC typically involves assessment of eligibility for surgery followed by

choice of surgery, chemotherapy, radiation therapy, or a combination of modalities as appropriate, depending on tumour type and stage.

2. For stage I and II disease,

• the standard approach is surgical resection with either lobectomy or pneumonectomy combined with mediastinal lymph node sampling or complete lymph node dissection.

• Surgery is curative in about 55 to 70% of patients with stage I and in 35 to 55% of patients with stage II disease.

3. Preoperative pulmonary function is assessed. Surgery is done only if NSCLC patients will have adequate pulmonary reserve once a lobe or lung is resected.

• FEV1 > 2 L generally tolerate pneumonectomy. • FEV1< 2 L should have a quantitative xenon radionuclide perfusion scan to determine the

proportion of function they can expect to lose as a result of resection. • Postoperative FEV1 can be predicted by multiplying percent perfusion of the non-resected

lung by the preoperative FEV1. • A predicted FEV1 > 800 mL or > 40% of the predicted normal FEV1 suggests adequate

postoperative lung function, although studies of lung volume reduction surgery in COPD patients suggest that patients with FEV1 < 800 mL can tolerate resection if the cancer is located in poorly functional, bullous (generally apical) lung regions.

1. Adjuvant chemotherapy after surgery is now standard practice for patients with stage II or stage III disease and possibly also for patients with stage IB disease and tumors > 4 cm.

• Clinical trials have shown an increase in 5-yr survival rates with the use of adjuvant chemotherapy. Adjuvant chemotherapy dependant on the patient’s comorbidities and risk assessment.

• A commonly used chemotherapy regimen is a cisplatin-based doublet (combination of a cisplatin and another chemotherapy drug, such as vinorelbine, docetaxel, paclitaxel). Neoadjuvant (preoperative) chemotherapy in early-stage NSCLC is also commonly used and consists of 4 cycles of a cisplatin-doublet. In patients who cannot receive cisplatin, carboplatin can be substituted.

2. Stage III disease is treated with either chemotherapy, radiation therapy, surgery, or a combination of therapies; the sequence and choice of treatment depend on the location of the patient's disease and comorbidities.

• In general, chemotherapy and radiation therapy are standard treatment for unresectable stage IIIA disease,

• Patients with stage IIIB disease with contralateral mediastinal nodal disease or supraclavicular nodal disease are offered either radiation therapy or chemotherapy or both.

• The 5-yr survival rate for patients with treated stage IIIB disease is 5%.

Types of surgery 1. Lobectomy and pneumonectomy

• The standard surgical approach remains a lobectomy, which helps preserve pulmonary function.

• Hilar and other proximal tumours may require more extensive surgery,

2. Wedge resection/segmentectomy

• Sublobar resections are used for patients with poor pulmonary reserve and are increasingly being used in conjunction with video-assisted thoracoscopic surgery (VATS).

• A review of SEER data from 1988-2008 found that the survival benefit of lobectomy over sublobar resection for stage I NSCLCs ≤ 2 cm in size decreased over that time.

• In patients older than 74 years with stage IA NSCLC, Okami et al found no significant difference in 5-year survival after sublobar resection versus standard lobectomy, although locoregional recurrence rates were higher after sublobar resection. A study by Wolf et al showed that sublobar resection is a reasonable option for elderly patients with compromised cardiopulmonary status

1. Video-assisted thoracoscopic surgery

• Video-assisted thoracoscopic surgery (VATS) is a minimally invasive surgical modality being used for both diagnostic and therapeutic lung cancer surgery. It offers low perioperative morbidity and mortality as well as decreased pain and hospitalization.

• Recurrence rates and 5-year and long-term overall survival appear similar to those with traditional open thoracotomies.

• This approach is also better tolerated in older populations. Finally, patients treated with VATS appear to have fewer delays and dose reductions in adjuvant chemotherapy.

2. Mediastinal lymphadenectomy

• The role of routine mediastinal lymphadenectomy versus lymph node sampling remains controversial. The authors of a large randomized trial recommend that an adequate mediastinal lymphadenectomy should include exploration and removal of lymph nodes from stations 2R, 4R, 7, 8, and 9 for right-side cancers and stations 4L, 5, 6, 7, 8, and 9 for left-side cancers.

1. Pneumonectomy: A surgical procedure in which an entire lung is removed. A pneumonectomy is an open chest technique (thoracotomy).

2. Lobectomy: It is a common surgical procedure that removes one lobe of the lung that contains cancerous cells. Removal of two lobes is called bilobectomy.

3. Wedge resection: A wedge resection is a surgical procedure during which the surgeon removes a small, wedge-shaped portion of the lung containing the cancerous cells along with healthy tissue that surrounds the area. The surgery is performed to remove a small tumor or to diagnose lung cancer.

• A wedge resection can be performed by minimally-invasive video-assisted thoracoscopic surgery (VATS) or a thoracotomy (open chest surgery).

• Sleeve lobectomy: A surgical procedure that removes a cancerous lobe of the lung along with part of the bronchus (air passage) that attaches to it. The remaining lobe(s) is then reconnected to the remaining segment of the bronchus. This procedure preserves part of a lung, and is an alternative to removing the lung as a whole (pneumonectomy).

• Segment resection: A segment resection removes a larger portion of the lung lobe than a wedge resection, but does not remove the whole lobe.

Survival • Stage 1: 5yr survival 75%

• Stage 2: 5yr survival 40%

• Stage 3: 5yr survival <30%

• Post-operative mortality rate: Lobectomy - 2%, pneumonectomy - 6%

References1. Slide 3: Merck manual:

http://www.merckmanuals.com/professional/pulmonary-disorders/tumors-of-the-lungs/lung-carcinoma

2. Slide 4: Merck manual: http://www.merckmanuals.com/professional/pulmonary-disorders/tumors-of-the-lungs/lung-carcinoma, Oxford: Clinical surgery,

3. Slide 5: Oxford: Clinical surgery

4. Slide 6: Image source - Robbins Pathology

5. Slide 7: Image source - Robbins Pathology

6. Slide 8: Table source: Merck manual http://www.merckmanuals.com/professional/pulmonary-disorders/tumors-of-the-lungs/lung-carcinoma

7. Slide 9 - 10: Table source: Merck manual http://www.merckmanuals.com/professional/pulmonary-disorders/tumors-of-the-lungs/lung-carcinoma

8. Slide 11: WebMD http://www.webmd.com/lung-cancer/ss/slideshow-lung-cancer-overview

9. Slide 13 - 14: Figure 1: http://www.aboutcancer.com/RUL_cancer.htm , Figure 2: http://www.aboutcancer.com/lung_ct_bmc_207.jpg

10. Slide 15 - 20 : Medscape SCLC: http://emedicine.medscape.com/article/280104-overview, NSCLC: http://emedicine.medscape.com/article/279960-overview

11.Slide 21 and 22: http://www.cts.usc.edu/lpg-typesoflungsurgery.html

12.Slide 23: Oxford: Clinical surgery