Lung cancer is the overall leading cause of cancer mortality in Canadian men and women. By the end of 2011, an estimated 25,300 new cases of lung cancer will be diagnosed in Canada. 1 In addition, an estimated 20,600 Canadian men and women will die from their disease; a total higher than the estimated deaths from prostate, breast, and colorectal cancers combined. 1 Despite many research and clinical advances in lung cancer treatments, the age-standardized five-year survival rate for all types and stages of lung cancer combined is only 16 percent for Canada overall, and 14 percent for Alberta. 1 The economic impact of lung cancer care is equally as staggering: the mean cost associated with the care of each patient diagnosed with lung cancer in Alberta is reported to be $15,350 for non-small cell lung cancer and $18,243 for small cell lung cancer, not including end-of-life care. 2 Smoking remains the largest single risk factor for lung cancer, responsible for 90 percent of lung cancers in men and 80 percent of lung cancers in women in Canada. Exposure to specific industrial and atmospheric pollutants, including second-hand tobacco smoke, also increases an individual's risk of lung cancer.
Lung cancer can be classified into non-small cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). NSCLC accounts for 80 percent of all lung cancer cases, and is categorized using the TNM staging system, which was recently updated by the International Association for the Study of Lung Cancer (IASLC). 3 The staging definitions and stage groups for NSCLC are summarized in a supporting document (NSCLC Staging System).

# GUIDELINE QUESTIONS
- What are the recommended treatment options for patients with operable stage III non-small cell lung cancer?
- What are the recommended treatment options with curative intent for patients with inoperable stage III non-small cell lung cancer? 3. When is palliation recommended, and what are the recommended palliative treatment options for patients with inoperable stage III non-small cell lung cancer?

# DEVELOPMENT AND REVISION HISTORY
This guideline was reviewed and endorsed by the Alberta Provincial Thoracic Tumour Team. Members of the Alberta Provincial Thoracic Tumour Team include medical oncologists, radiation oncologists, surgical oncologists, nurses, pathologists, and pharmacists. Evidence was selected and reviewed by a working group comprised of members from the Alberta Provincial Thoracic Tumour Team and a Knowledge Management Specialist from the Guideline Utilization Resource Unit. A detailed description of the methodology followed during the guideline development process can be found in the Guideline Utilization Resource Unit Handbook. This guideline was originally developed in July, 2008. It was revised in September, 2009 and April, 2012.

# SEARCH STRATEGY
For this guideline update, the working group conducted a search for new or updated practice guidelines published since September 2009 by accessing the websites of the following organizations: Cancer Care Ontario, the British Columbia Cancer Agency, Cancer Care Nova Scotia, the National Comprehensive Cancer Network, the American Society of Clinical Oncology, the Scottish Intercollegiate Guidelines Network, the National Institute of Health and Clinical Excellence, the American College of Chest Physicians, the European Society of Medical Oncology, Irish Journal of Oncology and Cancer Council Australia.
Medical journal articles were searched using the Medline, Cochrane Database of Systemic Reviews, and PubMed electronic databases. The search term "non small cell lung cancer stage III" was searched, including related terms. Limits placed on the search included: publication between 2008 and present, "meta-analysis", "clinical trial", "randomized controlled trial", "clinical trial, phase III", "clinical trial, phase IV", "controlled clinical trial", "humans", and "English". Results were further excluded if they were phase I or II clinical trials, included less than 100 patients with stage III non-small cell lung cancer (in clinical trials), were not related to treatment, focused only on the treatment of metastases, did not include an analysis of outcomes achieved by patients with stage III disease and did not discuss survival. The reference lists of relevant Cochrane reviews and guidelines by ACCP and NCCN were scanned to further identify relevant phase III clinical trials.
The working group reviewed the acceptability and findings of all relevant literature and updated the guideline for the treatment of stage III non-small cell lung cancer. A draft of the guideline was then circulated to the entire provincial tumour team for final feedback and approval.

# TARGET POPULATION
The recommendations in this guideline apply to adult patients over the age of 18 years.
- Whenever possible, patients should be considered for eligibility in ongoing clinical trials.
Treatment for Operable Disease (T3N1, selected T4N0-1) 2. Surgical resection is recommended. 3. Extended pulmonary resection may be performed in selected lesions. These include peripheral lesions invading the chest wall, apical lung carcinomas, central lesions with limited mediastinal invasion, or focal pericardial or phrenic nerve invasion. Carinal tumours and those within 2 cm of the carina occasionally may be amenable to resection with airway reconstruction. 4. Platinum-based chemotherapy regimens are recommended as post-operative adjuvant therapy in the management of patients with completely resected stage IIIA NSCLC.  Cisplatin-based treatment is preferred, although carboplatin-based regimens can be used as an alternative if there is a contraindication to cisplatin. 5. Adjuvant radiotherapy after surgical resection is not routinely recommended. However, this treatment could be considered when there is microscopic involvement of the resection margin, including the bronchial resection margin.
Curative Intent Treatment for Inoperable Disease 6. Combined concurrent chemo-radiation is recommended for inoperable stage III patients with good performance status (ECOG 0-2), minimal weight loss, good pulmonary reserve, and tumour and anatomy conformation permitting radical dose radiation without expected severe normal tissue toxicity.  Cisplatin-based chemotherapy (with either etoposide or vinorelbine) and thoracic radiation of 55Gy in 25 fractions to 66Gy in 33 fractions is the recommended treatment option.
- For patients with borderline performance status or moderate weight loss (5-10%), concurrent or sequential chemo-radiation or higher dose hypofractionated radiation are options.
Treatment for T1-3N2 Disease 8. Concurrent chemo-radiation is recommended for pre-operatively diagnosed N2 disease. Cisplatinbased chemotherapy (with either etoposide or vinorelbine) and thoracic radiation of 55 Gy in 25 fractions to 66 Gy in 33 fractions is the recommended treatment option. Additional cycles of chemotherapy can be considered for bulky disease. 9. In select patients, neoadjuvant chemoradiotherapy followed by lobectomy can be considered. Preoperative pathologically diagnosed N2 disease is not recommended to undergo surgical resection alone. 10. For patients with N2 disease discovered intra-operatively where complete resection of the lymph nodes and primary tumour is technically possible, completion of the planned lung resection is recommended. 11. In patients with N2 disease discovered intra-operatively, platinum-based adjuvant chemotherapy is recommended. Adjuvant radiotherapy can be considered in select patients.

# Palliative Treatment for Inoperable Disease
- In patients where lung reserve precludes radical radiotherapy, palliative chemotherapy and/or palliative radiotherapy are recommended. 13. Palliative chemotherapy options include:  1 st line: platinum-based doublets  2 nd line: docetaxel, erlotinib or pemetrexed 14. For symptomatic patients with poor performance status (ECOG>2) and/or significant weight loss (usually defined as >10% in previous 3 months), radiotherapy for symptom palliation is recommended. Dose-fractionation schedule options include:  20Gy in 5 fractions or 30Gy in 10 fractions  Single fractions of radiotherapy less than 10Gy may be appropriate in some clinical circumstances such as poor performance status or patient travel distance.  Split course radiation can also be used in select cases.