ED08.01 Surgery of Early-Stage NSCLC

Abstract

Early stage lung cancer — a term in transition generally early stage lung cancer is understood as stage I and stage II non-small lung cancer. An alternative understanding of early stage lung cancer is resectable disease. However, both definitions are imprecise and subject to development and Expertise. 1. Defining early stage lung cancer as resectable disease depends on regional philosophies and local expertise and therefore is the most unreliable and variable definition. The term resectability focuses on the T factor of the tumor and describes the ability of the surgeon to achieve radical resection. In contrast operability includes any potential regional and systemic spread and focuses more on the N and M descriptors. 2. Defining early stage lung cancer based on mediastinal nodal involvement neglects the fact, that single station N2 (N2a) is associated with the same five-year survival as multistation N1 (N1b). This touches on the term locally advanced disease, which in fact also means different things for different people. For the oncologist locally advanced disease usually means N2 involvement with the consequent call for chemotherapy. For the surgeon locally advanced disease primarily addresses the T factor and is used for T3 or T4 tumors, indicating more extended resections in the absence of N2 disease. In summary, terms like early stage, locally advanced stage or advanced stage should be avoided since they do not properly describe a clinical situation nor are they guiding therapy. If the term early stage lung cancer should be maintained for any reason, there is need for revisions. The five-year survival of stage I and stage II non-small lung cancer is a range of less than 30 to more than 90% and the survival expectedly mainly depends on nodal involvement. The estimated median five-year survival of patients with screening detected T1N0 NSCLC is a reported 92%. Even nodal negativeT3 tumors are associated with almost 60% five year survival following radical resection. On the other hand involvement of multiple N1 lymph nodes results in a much worse prognosis of about 35%. However, for this presentation the current definition of stage I and stage II non-small lung cancer was used. Resectability of lung cancer for technical reasons in general, and in early stage lung cancer in particular, very rarely is an issue. Oncological operability has to be defined preoperatively along international guidelines. The European Society of Thoracic Surgeons (ESTS) recently has published revised guidelines for preoperative mediastinal lymph nodes staging for non-small cell lung cancer. Only one selected group of patients with tumors of less than 3 cm in diameter (cT1) in the outer third of the lung without signs of nodal involvement at CT scan, PET scan or PET CT (cN0) may directly undergo surgical resection. All other clinical situations require invasive preoperative staging by bronchoscopy plus EBUS/EUS. If the absence of nodal involvement is verified by EBUS/EUS this patient may also directly undergo surgery. In the presence of radiologically suspect mediastinal lymph nodes and negative EBUS/EUS further confirmation is recommended using mediastinoscopy or thoracoscopy. If mediastinal nodal involvement is histologically verified by any means the patient has to undergo multimodality treatment. All clinical findings are to be discussed in an interdisciplinary tumor board for proper therapy planning.1 Surgery remains the cornerstone of treatment of early stage non-small lung cancer for patients willing to accept the procedure-related risks. Goal of any surgical intervention for early stage lung cancer is the complete resection of the primary tumor together with regional lymphatic nodes. The standard for any resection with curative intent is defined by anatomical lung resection. In early stage lung cancer the predominant type of resection is lobectomy or bilobectomy, sometimes along with bronchoplastic or angioplastic procedures or extended resections for locally invading T3 tumors. Pneumonectomy particularly in the treatment of early stage lung cancer is rarely used. Gold standard of surgical resection for lung cancer is lobectomy. This standard is based on a prospective multi-institutional randomized trial comparing limited resection with lobectomy for peripheral T1N0 non-small cell lung cancer published in 1995.2 In the absence of more recent prospective randomized trials lobectomy still must be considered the surgical procedure of choice for patients with peripheral T1N0 non-small cell lung cancer. An extensive body of literature mainly composed of retrospective studies supports the use of radical anatomical segmentectomy for peripheral cT1N0M0 non-small lung cancer with less than 2 cm in diameter, certainly for older patients with limited cardiopulmonary function. However, caution should be taken to promote a widespread indication for intentional segmentectomy in young good surgical candidates until the results of the ongoing randomized controlled trials become available.3,4 Minimally invasive anatomical resection for lung cancer carried out by means of video-assisted thoracic surgery (VATS) has been increasingly carried out during the past years. A systematic review and meta-analysis of randomized and nonrandomized trials published in 2009 reported an improved five-year survival and reduced systemic recurrences in patients who received VATS lobectomy.5 A multicentric propensity-matched analysis of more than 1000 patients, of which 700 had undergone VATS lobectomy confirms, that thoracoscopic lobectomy is associated with lower morbidity as compared with thoracotomy. The positive impact of minimally invasive surgery in the treatment of lung cancer particularly applies to the elderly.6 Regarding long-term survival after video-assisted thoracoscopic lobectomy a meta- showed a survival benefit in the favor of VATS with a difference in survival of 5% at five years. The reason for this observed survival benefit may be attributed to a less pronounced compromise of the immunocompetence after the surgical trauma.7 The rationale for a formal mediastinal lymph node dissection is multifold. The distribution pattern of mediastinal lymph node metastasis is not predictable and skip metastasis are seen in up to 30% of patients. Even small tumors may present with unexpected N2 disease with an incidence of 6-10%. The operative morbidity is not significantly influenced by a systematic mediastinal lymph node dissection. Recommended standard of mediastinal lymph node dissection is the removal of all mediastinal tissue containing lymph nodes in a systematic Approach within anatomical landmarks. The most recent randomized controlled trial published in 2011 did not find a survival benefit by complete mediastinal lymphadenectomy in patients with early stage lung cancer, but the results should not be generalized to patients staged only radiographically or those with higher stage tumors. The recommendation from this study is that a formal mediastinal en-bloc dissection may still affect survival and certainly optimally stages patients. In the subgroup analysis no difference between VATS and open lobectomy was observed for number of lymph nodes harvested and regarding long-term survival.8 As minimally invasive surgery along with unilateral mediastinal lymphadenectomy generally prolongs operation times and the requirement of single lung ventilation the advantages for the elderly population has to be questioned and discussed individually. An alternative to thoracoscopic unilateral lymphadenectomy is offered by video-assisted mediastinal lymphadenectomy through the neck (VAMLA). The approach is similar to transcervical mediastinoscopy and allows for a radical bloc dissection of all mediastinal lymph node stations. Besides the benefit of bilateral lung ventilation during this phase of the operation a bilateral mediastinal lymphadenectomy offers improved surgical radicality. In patients unfit for surgery SABR is the treatment of choice for peripherally located stage I non-small cell lung cancer. If SABR is not available a hypofractionated radiotherapy is advocated. A systematic Review comparing outcomes of SABR and surgery in patients with severe COPD revealed a higher 30 day mortality following surgery but similar overall survival at one and three years.9 In a meta-analysis of 19 out of 318 papers with the best evidence addressing a comparison of SABR and surgical wedge resection both methods proved as reasonable alternatives to lobectomy in high risk surgical patients. In this analysis SABR was associated with reduced local recurrence compared to wedge resection and should be considered when wedge resection is planned due to anatomical location and size of the primary tumor in a patient who is high risk for surgery.10 Although local tumor control may be comparable or even superior to extra-anatomic surgical resection a quite high rate of late radiological changes after stereotactic ablative radiotherapy for early stage lung cancer has to be considered. At one year follow-up the predicted probability of having expected or pronounced radiological changes after SABR were 65 and 22%. These changes included phenomena like mass-like appearance, radiation fibrosis, and rib fractures, which sometimes are difficult to differentiate from tumor recurrence. The ACCP guidelines address the question, who had to be considered a high risk candidate for surgery. With the advent of minimally invasive resection, the criteria to classify a patient as too ill to undergo an anatomic lung resection are being redefined. Surgical resection remains the primary and preferred approach to the treatment of stage I and II NSCLC in patients with good or low surgical risk. Primary radiation therapy remains the primary curative intent approach for patients who refuse surgical resection or are determined by a multidisciplinary team to be inoperable.11 1. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R, Turna A, Van Schil P, Venuta F, Waller D, Weder W, Zielinski M. Eur J Cardiothorac Surg. 2014 May;45(5):787-98 2. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ginsberg RJ; Rubinstein LV. Ann Thorac Surg. 1995; 60(3):615-22; discussion 622-3 3. Tsutani Y, Miyata Y, Nakayama H, et al. Oncologic outcomes of segmentectomy compared with lobectomy for clinical stage IA lung adenocarcinoma: propensity score-matched analysis in a multicenter study. J Thorac Cardiovasc Surg 2013;146:358-64. 4. Zhao X, Qian L, Luo Q, et al. Segmentectomy as a safe and equally effective surgical option under complete video-assisted thoracic surgery for patients of stage I non-small cell lung cancer. J Cardiothorac Surg 2013;8:116, 5. Yan TD, Black D, Bannon PG, McCaughan BC. Systematic review and metaanalysis of randomized and non-randomized Trials on safety and efficacy of videoassisted thoracic surgery lobectomy for early-stage non-small cell lung cancer. J Clin Oncol 2009;27:2553-2562 6. Thoracoscopic lobectomy is associated with lower morbidity compared with thoracotomy.Villamizar NR, Darrabie MD, Burfeind WR, Petersen RP, Onaitis MW, Toloza E, Harpole DH, D'Amico TA. J Thorac Cardiovasc Surg. 2009 Aug;138(2):419-25. 7. Long-term survival in video-assisted thoracoscopic lobectomy vs open lobectomy in lung-cancer patients: a meta-analysis. Taioli E, Lee DS, Lesser M, Flores R. Eur J Cardiothorac Surg. 2013 Feb 14. 8. Darling GE, et al. Randomized trial of m diastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 less than hilar) non-small cell carcinoma. J Thorac Cardiovasc Surg 011;141:662-70 9. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, Treatment and follow-up. J. Vansteenkiste, D. De Ruysscher, W. E. E. Eberhardt, E. Lim, S. Senan, E. Felip & S. Peters, on behalf of the ESMO Guidelines Working Group 10. Mahmood S, Bilal H, Faivre-Finn C, Shah R. Is stereotactic ablative radiotherapy equivalent to sublobar resection in high-risk surgical patients with stage I non-small-cell lung cancer? Interact Cardiovasc Thorac Surg. 2013 Nov;17(5):845-53. 11. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Howington JA, Blum MG, Chang AC, Balekian AA, Murthy SC. Chest. 2013 May;143(5 Suppl) early stage lung cancer, thoracic surgery, VATS lobectomy, VAMLA