Resection of Non-small Cell Lung Cancer

Resection of Non .:.small Cell Lung Cancer* How Much and by What Route Hobert j. Gi nsberg ,

ut:

FCCP

Surgical resection remains the preferred treatment, when possible , in patients with non-small cell lu ng cancer (NSCLC). A comp lete resecti on is requi red to p ot e ntiall y im prove survival of these patie n ts. Lobectom y is the min imum r esection of choice. En bloc resections of involve d adjacen t organs and struct ures are pe rformed routi nely with accep tab le morbidity a nd mortality. Medias ti nal lymph n ode di ssection allows accurate su rgical and p athol ogic staging of lymph node di sease but h as ye t to b e p roven effic acio us as a curative procedure. The sta n dar d ap proach to the h emithorax is via poste rolateral thoraco to my. Rec ent muscle- sp aring in cisions and videoass isted techn ique s have b een e mp loyed sa fe ly to accomp lish goals of su rgery. Th is a rticle evalu ates p ast a nd current approaches to the resectio n of NSCLC, a n d looks at the im pact of route a nd extent of resecti on on survival of NSCLC p atients. (CHEST 1997; 112:203 5-2055)

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ompleteness of resection is the ultima te goal of sur gical resection in the managem ent of lung cancer. Following its introduction by Graham and Sed al,' pn eu monectomy became the standar d approach to resection of lung cancer, no matte r th e stage of disease. Once surgeo ns developed the techniques of individual ligation of vessels and bronchi, it became evident that, for early-stage disease limited to one lobe, lobectomy could usually offer a complete resec tion, thu s preserving functioning pulmonary tissue." Segmental resections were championed 30 years later by Jensik et aP as a method of managing early-stage lung cancer; their results appeared similar to those seen with lobectomy. For many yea rs, wedge resections have been employed in an attem pt to preserve pulmonary function in compromis ed individuals and, on the whole, have been limited to treatm ent of small periph eral tum ors (T I NO). Th ese resections have always been conside red a compromise and have been reserved for pat ients with very limited pulmonary reserve.v? Extended resections we re originally introduc ed over 40 years ago. "Radical pneu monectomy" describ ed the proced ure that included intrapericardial dissection and removal of mediastinal lymph nodes en bloc with the surgical specimen. 10 This approach was first suggested when it was ' From the Department of SurgelY, Mem orial Sloan- Kett erin g Cancer Center and Corne ll University Medical College , New York.

Reprint requests: Robert j. G insberg , MD, FCCP, Mem orial Sloan-KEttering Cancer Cente r, 12 75 York Ave, N ew York , NY 10021

realized that local rec urr ence was a majo r proble m in locally advanced disease, especially with incompl et e resections. En bloc resections of tum ors invading adjacent structures have become commonp lace, especially for lesions invading the che st wall (eg, T3 ches t wall tu mors, superior sulcus tumors). As with other lung cance rs, the over ridin g prognostic factor has always been a complete resection with negative resection margins.J J,l2 Cahan et aP3 wer e the first to introdu ce the con cep t of mediastina l lymph node dissection. This approach was used espec ially in patients with hilar or med iastina l lymph node disease in an attem pt to completely resect all obvious tumor with the goal of imp roving ultim ate survival. With this approach, advocates have claimed super ior .S-yea r survival rates, even in patients harbori ng N2 disease, as long as a complete resection can be accomp lished.w -" As with other tu mors , incompl ete resections have failed to yield many long-term survivors. As a result of work by the Lung Cancer Study Group (LC SG), \ 6 minimum intraoperative staging now requ ires selective biopsy of all ipsilateral med iastinal nodal stations withou t a complete lymph node dissection when N2 disease is not present. Most recently, exte nde d lymph node (two-field) dissections have been advocated by a variety of surge ons in Japan, who suggest this approach will yie ld bett er long-term survival in advanced as well as early-stage disease compared with historical d ata . l 7. 1 ~ Although ante rolate ral thoracotomy was the first appro ach used to attempt pul monary resection via the hem ithorax, posteri or and posterolater al approaches quickly became commonplace in resecting these tu mors. By the I950s, posterolateral thoracotomy was the incision of choice. More recently, ste rnotomy, hemi-clamshell incisions , and full clamshell incisions (transverse ste rnotomy) have also been used in special circumstances.w-? In an atte mpt to decrease postoperative pain, mu sclesparing incisions, championed by Kittle,21 have now emerged as viable opti ons th at still allow full access to the hem ithorax by ope n thoracotomy.v -> Video-assisted techniqu es have also been e mployed to furthe r decrease postoperative pain, red uce hospital stays, and improve cosmesis. In the past 5 yea rs, video-assisted surgery has evolved to the point at which complete resections can be accomplished using stand ard hilar dissection teclmiqu es.s! Mediastinal lymph node sampling and dissection can also be perform ed safely.P

How M UCH ?

Extent of Dissection The re is now sufficient evide nce from retrospective ana lyses and a recen tly reported LCSG prospective randomized trial to support the use of lobectomy as minimum resection even for the earliest-stage lun g cance r in otherwise fit patien ts. When lesse r resections are employed, the risk of local recurren ce in patients with TI NO disease is appro ximately thr eefold as compa red with lobectomy in most series.26.27 For this reason, lobectomy should continue to be the resection of choice, except in seve rely CHEST / 112/ 4 / OCTOBER, 1997 SUPPLEMENT

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compromised individu als. This has been substantiated by anatomic studies of lymphatic drainage demonstrating evide nce of occult lymph atic permeati on proximal to the tumor, even in tumors sur gically staged as T1 NO, in up to 15% of cases.2S -:l O In patients severely compromised by poor pulmonary function, the lesser resection of choice, whenever possible, should be segmentectomv, which allows re moval of lvmphatic channels and lymph nodes, draining the tu mor bed . In the recent Lcse report .?" segmentectomy appea red to be associated with a lesser chan ce of local recurrence than wedge resection , although these subsets were too small to gauge statistical significance. The use of wedge resection in the managem ent of lung cancer must be conside red a compromise, regardless of the size or stage of the tumor. Most report s of satisfactory results with wedge resection have also added postop erative radiother apy to the ipsilatera l hem ithorax and mediastinum.>" Althou gh late follow-up of such patients has not included pulmonary function analysis, other studies have demonstrated a late adverse effect of postop erati ve radioth erap y on pulmonary function . In reality, postoperative radiotherapy produces a "slow lobectomy" due to pulmonary fibrosis. A new approach in the managem ent of COPD- lung reduction surgery-produ ces improv ed pulmonary function in severely compromised pati ents ." These results call into qu estion the whole concept of how large a resection such patient s can tolerate, and whether the condition of even sever ely compromised patients might be impro ved by a "lung-reducing" lobectomy. For tu mors invading adjacen t struct ures, an ell bloc resection of the adjacent involved area is not only advisable but necessary. Th is may include the following structur es: chest wall, contents of the superior sulcus, supe rior ve na cava, pericardium, intraperi cardial major vessels, lower trachea and carina, esophageal wall, vert ebra, or diaphragm. 29 .3 o All of the above-m entioned stru ctures may be resected and the anatomy reconstituted with only minim ally increased morbid ity and mortality. Wherever possible, these resection s should be performed ell bloc, avoiding any trans gression of the tumor at the time of surgery. Even in peripherally placed T3-4 tumors, a recent retrospective analysis of superior sulcus tumor resections at Memorial Sloan-Kett ering Cancer Center concluded that a large wedge resection yielded a lesser cha nce of ultimate survival than a standar d lobectomy.P

Mediastinal Lymph Node Dissection vs Lymph Node Sampling The minimum acceptable resection in the management of lung cancer must includ e adequate lymph node sampling of hilar and ipsilateral mediastinal lymph nodes for the final pathologic staging requ ired for accurate assessment of pro gnosis and possible need for adjuvant therapy. To our knowledge, no study has conclusively demon strated any survival advantage for a complete mediastinal lymph node dissection .P Our expe rience has been that this pro cedure adds very little morbidi ty, increased operating time, or effort . Th erefore, for the most compl et e 2045

surgical and final pathologic staging, we believe that complete ipsilateral mediastinal lymph node dissection (vs sampling) should be consider ed a routin e part of the oncologic surgical pro cedure. This will also ensure the best chance for complete resection of all tum or present in the hemithorax.w" Extended lymph node dissection to include contra lateral mediastinal and supraclavicular lymph nodes has been adopted as the treatm ent of choice by some surgeons in [apan. '•.IS As yet (to our knowledge ), there has been no prospective rand omized trial to dem onstrate impro ved survival with this modified procedure. However, compared with historical data, surgeons employing this technique have claimed improved 5-yea r surviva l for patients ultimately identifi ed to have N3 diseaseY ·Is Only a very large rand omized trial will confirm the efficacy of lymph nod e dissection , be it limited to the ipsilateral hemithorax or exte nded to includ e all mediastinal and supraclavicular lymph nodes.

By WHAT

ROUTE?

Th er e is no doubt that a gene rous posterolateral thoracotomy or, when indicated , anterior approache s by sternotomy or clamshell incisions (transverse stern otomy) vields the best access to intr athoracic conte nts. The avail~lbi lity of improv ed pain-relieving techniques (eg, epidural analgesia), allowing decreased postoperative morbidity, has made these incisions less form idable. Muscle-sparin g incisions have also been used to clecrease postoperative pain and improve cosmesis, but these can compromise exposure and exte nsibility, ther eby limiting their use. To our knowledge, ther e has yet to be a conclusive randomized trial to prove the efficacy of muscle-sparing incisions in minimizing postoperative pain or impro ving cosmesis. Th e recent inter est in video-assisted techniques has spurr ed some surgeons to e mploy methods of resection (eg, wedge excision or lobar resections without adequate lymph node dissection or samplin g) that are less than satisfacto ry, even in early-stage disease, because of the risk of leaving occult lymphatic disease.:l4 ·35 However, oth er surgeons, more adept at video-assisted techniques, have accomplish ed standard lobectomies, pneumonectomies, and mediastinal lymph node samplin g and dissection .w-" For the most part, video-assisted approaches have been reserved for very- earl y-stag e tumors requiring uncomplicated resections. Despite the claims of improv ed cosmesis, acute and chronic postop e rative pain relief, and redu ced hospital stays, rand omizecl trials to date (and to our knowledge ) have failed to demonstrate any advantages for video-assisted surgery other than improved cosme sis.?" CONCL USIO NS

Surgical resection for lung cancer remains the tr eatment of choice whe never possible. A complete resection is req uired. Lobectomy is the minimum resection of choice, with lesser resections being reserved for only the most severely compromised individuals. Ell bloc resection of involved adjacent organs and structures can be accomplished with acceptable morbidity and mortality, allowing complete resec tions to occur . Th e addition of mediastinal lymph node dissection produces the best possible surgical Mult imodality Therapy of Chest Malignancies-Update '96

and pathologic staging of lymph node disease but has yet to be proven more efficacious as a curative procedure. Th e role of extende d (N3) lymph adenectomy has yet to be defined . Although posterolateral thoracotomy re mains the standard approach to the hemithorax, more recent muscIesparing incisions and video-assisted approaches have been safely used to accomplish many of the above-mentioned resec tions. When necessary, ste rnotomy, transverse sternotomy, and combinations of these two can be used to improve access to anterior-situated tum ors. R E F ER E NC ES

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