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Large Cell Carcinoma ofthe Lung: a Contribution on Prognosis after Potentially Curative Resection H. Huuier', H. W Donie', I. Vo lkme r' , and G. Seit z! Depa rtm ent of Thoracic and Ca rdiovascula r Surgery Institute of Pat hology. Saa rland University Hospital, Hombur g/Saa r, Germany

Sum mary Between 1976 and 1989. 53 out of 60 patie nts with large cell ca rcinoma of t he lung underwent poten tially curative surgery. i. e. macroscopically and microscopica lly complete resection. For bette r comparison , all tumors were classified according to the TNMstagi ng sys tem of the Ulf.C 4 th editio n of 1987. Following potentially cur ative surgery, in stage 1the mean survival time was 19 mo nths and the five-year surv ival rate 30 .1 'Yo, in stage II 8 mont hs an d 10% , an d in stage lIla 6.5 months and 0 %, respectively. The dilTerences in the long term prognosis betwee n the tum or stages are significant. No significant differences could be demo nstrated between II a nd lila in terms of the mea n survival times . The prognosis for patients with potentially curatively resected sq uamous cell ca rcinoma is significa ntly better tha n that for patients with la rge cell ca rcinoma. Key word s

Die Pro gnose der Patien ten nach poten tiell ku rat iver Besektion grollze llige r Bronch ialka rzinomc 53 von 60 Patie nte n mit groBzelligem Kar zinom der Lunge konnten in den Ja hren 197 6 bis 1989 potenti ell kur ativ ope riert werden . Zum besseren Vergleich wur de das Stag ing aller Tu more n einheitlich nach dem TNM-Schema de r4 . Autlage der UIeC von 1987 vorge nomme n. Die mittlere Oberlebensze it nach potent iell kura tiver Operatio n betrug im Stadium I 19 Monat e. die fi -Ja hres -Uberlebensquote 30 ,1 %, im Stadium 11 8 Monat e bzw. 10,0 % und im Stadium IlIa 6,5 Monate bzw . 0 %. Die Unterschiede der Sc.Iahres-Dberlcbonsraten zwischen den Tumorstadien sin d sig nifika nt. Die Kurzzeitprognose bet reffend finden sich signifikante Untersc hiede zw ische n den Tumorsta dien I und II sowie I und lIla. Die Progn ose von Patienten mit potentiell kura tiv reseziertern Plattene pithelkarzi nom ist signifikant besser als die Prognose von Patient en mit groBzelligem Karzinom.

La rge cell carci noma - Prog nos is after su rgical thera py

Introduction Most authors put the frequency of lar ge cell carcinoma at about I 0 %. There a re differing opinions as to the prognosis for patients suffering from this histological type of bronchial ca rcinoma . Some authors see it as being as good as the prognosis after surge ry for squamous cell ca rcinoma (4, 6, 9, II) while others view it as clea rly worse 0 , 2, 7,1 3). We report on 53 pat ients who under went potenti ally cur ative su rgery on large cell carcinoma an d compa re their survival times with those of patients with squa mous cell car cinoma . By the term "potentially cura tive surgery" we understand macroscopically and microsco pically complete resection. Mat er ials and Methods Between 1976 an d the en d of 1988 , 66 patients with large cell bronchial carcinoma were ope rated on in our clinic. A stu dy at the begi nn ing of 1989 elicited usab le information from 60 cases. Five women and 55 men were tre ated. The average age at the time of opera tion was 56 years , the youngest patien t being 39 a nd the oldest 75 yea rs old . Ta ble 1 shows the differen t ope rative procedures undertaken .

Thorac. cardiovasc. Surgeon 39 (199 1) 218-220 © Georg Thieme Verlag Stuttgart- New Yor k

Table 1

Distribution of the kindsof curative resection

l obectomy Bilobectomy Pneumonectomy

34 3

16

(64.1 %) ( 57 %) (30.2%)

The [mal diagnosis "large cell carcinoma " was esta blishe d by means of br onchoscopy 10 times (16.7 %), by tra nst ho racic puncture 8 times (13.3 %) a nd on operation in 42 cas es (70.0 %). The tu mors were more or less evenly located : left side 28, a nd right side 32 times . The sizes of the tu mors (meas ure d at th e widest diameter) lay between 1.2 and 12 em. Carci nomatous lymphangiosis was prese nt in 8 cases (13.3 %) an d a spread of tumor cells into a vesse l in four cases (6.8 'Yo), All pat ients with mediast inal lymph node involvement underwent postope rative ra diat ion tr eat me nt. as did those undergo ing palliative rese ction . The tumors have been classified acco rdi ng to the WHOcriteria (new WHOclassification 1981) . Large cell ca rcinoma is defined as a maligna nt epithelial tum or with large nuclei, prominent nucleo li, a bunda nt cytoplasm , a nd usually well-d ema rcated cell borders a nd witho ut characteristic feat ures of squa mous cell. small cell tumors , or adenocarcinomas.

Received for Publ ication: April 25,1 991

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Thome. eardiovase. S urgeon 3 9 (1991)

Large CellCarcinoma ofthe Lung

Results Out of the 60 patients with comp lete follow-up reco rd s, 53 (I, e. 88. 3 %) could be potentially curatively operated on. Three out of 60 patien ts (5%) died within the first 30 postop erative da ys. The causes of death were hemo rrh age , bron chus stump insufficiency, and pulmonary embolism . The cau ses of deat h for the gro up of patients und ergoing potentially curative surgery who died after the first 30 postoperative da ys we re meta stases (24, or 47 %), local reccurence of the tumor (I I , or 22 %) and unrelat ed diseas es (7, or 17 %). Nine pati ents were still alive at th e time of th e study. The mean survival time of potentially curatively operated patients was 14 .5 months and the S-year survival rate was 17 .0 %, wh ere as the me an su rvival time after incomplete res ection was only 2.8 months and nobo dy in this group survived five years. The differences are statistically significan t. The following resu lts include only those patients who underw en t potentially curat ive surgery. There were sta tistica lly significant differen ces am ong the various tumor stages in terms of 5-year survival rates (Table 2). No significant differenc es could be de monstrated bet ween II and lil a in terms of th e mean survival times. Using the TNM system (Table 3) the prognostic gradient fro m th e ea rly to th e advanced stages can be clearly see n. The differen ces ar e only partially significant, primarily due to the small number of cases. In Tab le 3, 9 pat ients with T2N I and 5 patients with T2N2 disea se a re shown. The mean survival times (7.7 and 7.3 month s, respectively) of thes e pati ents hardly differ and a re clearly sho rter than those of patient s with stage T3NO. This can be explained by the fact that in th e ' 70s lymph ad enectom ies we re not consistentl y carried out , so tha t some N1 case s were , in fact, in sta ge N2. To date, three patients have survived the opera tion for 10 years . These patients were in stages Tl NO, T2NO and T2NI , respectively, wh ereby the NI disease was a small central met astasis in a single bronchopulmonar y lymph nod e. Amo ng th e 53 potentiall y cura tively operated patie nts the re we re 9 patien ts with th e histological type of giant cell carcinoma (four patients in stage I, four in II, an d one in lil a). The me an surviva l tim es of these patients are not significantly shorter than those of patients with othe r types of large cell carcinoma . Discussion The frequency oflarg e cell carcinoma of the lung accoun ts for less th an 10 % in th e operative statistics of most authors and repr esents about 7.5 % of our pati ent population. In th e light of these relativ ely small tota ls only limited state ments have been mad e conce rning the prognosis for these tumors, and they differ considerably. There is overall agreement th at the pro gnosis is primarily dependent on th e tum or sta ge (2, 4, 6, 8, 9, II, 12). Five-year survival rates of between 20 % and 60 % are given for tumo r stage I (7, 8, 9,12 , 13). The same rates vary between 0 % and 18% for tumo r stage lil a (2, 8 , 9, 10). The conside rable vari ation is du e on the one hand , as alrea dy stat ed , to the limited material and on the other to the fact

Table 2 Mean survival times and five-year actuarial survival rates in the varioustumor stages Stage I

II

Ili a

n

Meansurvivaltime (months)

Five-year survival (%)

28 10 15

19.0 8.0 6.5

30.1 10.0 0

Table 3 Mean survival times in thevariousTNM stages TlNO T2NO TlNl T2Nl BNO TlN2 T2N2 BN2

n

Mean survival time (months)

7 21 1 9 5 0 5 3

29.4 18.5 17.5 7.7 12.5 7.3 1.5

Table 4 Mean survival times in the various tumor stages of large cell and squamouscell carc inoma

Stage

I

Large cell carcinoma n meansurvival time(months)

28 10 15

II

Ilia

19.0 8.0 6.5

Squamous cell carcinoma mean survival n time (months)

157 99 111

85.8 32.2 13.7

Table 5 Five-yea r survival rate in the various tumor stages of large cell and squamous cellcarcinoma Stage

Large cell carcinoma five-year n survival (%)

Squamous cell carcinoma five-year n survival (%)

I II

28 10 15

157 99 III

Ili a

30.1 10.0 0

60.8 31.6 13.4

that poorly differentiated large cell squamous can cers an d adenocarcinomas were not excluded (2). In our pa tient populatio n the prognosis following potentially curative res ection oflarge cell carcinoma is considerab ly wor se than that following the sa me ope ration for squa mous cell carcinoma, whic h we reported in an ea rlier study (3) (see Tab les 4 and 5). The differences in the mean survival times an d the five-year survival rat es in the equivalent tumor stages for lar ge cell an d squamous cell carcinomas are significant. This higher ma ligna nt potency of the large cell carcinoma is confirmed in severa l othe r pa pe rs (I , 2, 14). As with squa mous cell carcinomas, followin g potentially curative resection TNM stag ing ha s the highest prog nostic value. Refer en ces I

A/ba in. K. S.. L. D. True. H. M. Golomb. P. C. Hoffm an n. and A. G. Little: Large cell carcinoma of the lung. Ultrastructural differentia tion and clinicopath ologic correlations. Cancer 56 (1985)

2

Downey. R. S.. C. It: Sewell. and K. A. Mansour: Large cell car-

1618-1623 cinoma of the lung: a highly aggressive tumor with dismal prognosis. Ann. Thorac. Surg. 47 (1989) 806-808

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For better com pa riso n. the tum or stages were all cla ssified accor din g to the 4 lh edition of the UICC 198 7 TNM syst em. The lifetabl e met hod was used for sta tisti cal a na lysis.

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Thome. eardiolJase. Su rgeon 39 (J 99 1) Hutoer. 11.. I. Volkmer. R. Huls etoede. and F. Hous inqer: A contribution on the prognostic significance of the tumor formu la {pTNM} in squa mous cell carcinoma ofthe bronchus. Thorac. cardiovasc . Surgeon 37 (19891 281 -284 ~ Im m erm an. S. C . R. .\1. Vanecko. W. A. Fry. L. R. Hea d. and T. W Shields: Site of recurrence in patien ts with stages l und Ilcarcinoma of the lung rese cted for cure. Ann. Thorac. Surg. 32 1198 1123- 26 5 Kreyb erg. L.: Histological typing of lung tum ours . International histological classification of tumours. 1. Geneva. World Health Orga nization. t 967 . second edition 1981 (, Mart ini. N.. B. 1. Flehinge r. .\1. B. Zaman. and E. 1. Beattie: Prospective stud y of 445 lung carcinomas with mediastinal lymph node metasta ses. J. Thorac. Ca rdlovasc. Surg. 80 (19801390 - 399 1 stucnett. D. .\1.. P. G. M..vtorqan, and J. B. Ball: Prognostic featu res ofla rge cell ana plastic carcinoma of the bron chus . Thorax 35 (19801 118-122 8 Mountain . C F.: Assessm ent of the role of su rgery for control oflung cancer. Ann . Thorac. Surg. 24 {I 977) 365-373 9 Naruke. T.. T. Goya. R. Tsu ehiya. and K. S ue masu: Prognosis and survival in resected lung carci noma based on the neev· international staging system. J. Thorac . Cardiovasc. Surg. 96 (1988) ·H O-447 10 Nar uke. T.. T. Goya. R. Tsuch iya . and K. Suemasu: The importan ce of su rgery to non-small cell carcinoma of lung with mediastin al lymph node metasta sis. Ann. Thora c. Surg. 46 (1988) 603- 610 3

H. ttuicer. II. W. Donie. I. Volkmer. and G. S eitz 11

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cinoma : morbid implications of recurrent diseas e. Ann. Thorac. Surg.38( 1984)33 1-336 S hields. T. W .1. Yee. 1.11. Conn . an d C. D. Robinette: Relationship of cell type and lymph node metast asis to survival after resection of bronchial carcinoma . Ann. Thorac. Surg. 20 (1975) 501 -51 0 William s. D. E.. P. C. Pairotero. C. S . Daois, P. E. Bemotz, Iv. S . Payne. W F. Taylo r. M. A. Uhlenhopp. and R. S. Fontana: Surviva l of patients surgically treated for stage I lung cancer . J. Thorac . Cardiovasc. Surg. 82 (1981) 70-76 Yesn er. R.: The malignan cy of larg e cell lung carcinomas . Ann . Thorac . Surg. 47 (1989) 796-797

Dr. med. H. Huue r

Department of Thoracic an d Cardiovascular Surgery University of the Saa rland D-6650 Homburg/Saa r Germany

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