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CHEST I 89 1 4 I APR IL , 1986 I Supp lemen t 225S

A New In te rna tiona l S tag ing Sys tem fo r Lung C ance r*Cli f ton F M oun ta in , M .D ., FC .C .P

S tag ing oflung can cer acco rd ing to the TNM sys tem is anaccep ted p rinc ip le used by onco log is ts as a gu ide to

estim atin g p rogno sis and se lec ting trea tm en t in a g ivenpa tien t an d fo r repo rtin g end resu lts . Th e tw o m ost w ide lyused recom m enda tio ns fo r TNM classifica tion are tho se ofth e Am erican Jo in t C omm ittee on C ancer (A JCC )3 and th eUnion In terna tion a le C on tre C ancer (U ICC ) .4 A s in -vestiga to rs th ro ughou t the wo rld h ave pu t these stag ingsys tem s to wo rk , the need fo r re finem en ts to m ee t th e irin d iv idua l p rac tices has resu lted in varia tion s in the use ofthe cla ssif icatio ns. A p ro posa l now is m ade fo r a n ew andun iversal s tag ing system for lung cancer tha t is accep tab le tothe in te rna tio na l comm un ity charg ed w ith the resp ons ib ilityfo r u n ify ing s tag in g sys tem s (see A ppend ix ).

TH E TNM SY STEMT he TNM system , as o rig ina lly p ro posed by D eno ix ,

prov ides a cons isten t, rep roduc ib le desc rip tion fo r the an a-tom ic ex ten t o fd isease in cancer p atien ts a t a specific tim e inth e life h is to ry of th e can cer. C lin ica l s tag ing is the bes testim ate o fd isease ex ten t m ade prio r to the institu tion of anyth erap y ; su rg ical-p atho log ic stag ing is the c lassifica tion o fd isease ex ten t as d ete rm ined from patho log ic exam ina tion o fresec ted spec im ens . T he le tte r T rep resen ts the pr im arytum or an d num erica l su ffixes descr ib e in creas in g s ize an din vo lvem en t o r bo th . T he N ca teg ory represen ts reg io na llym ph nodes w ith app ropria te su ffixes to desc rib e leve ls o fm etas ta tic d isease . T he le tte r M represen ts d istan t m etas -tasis w ith approp ria te su ffixes to desc ribe the ab sence orp resen ce of m etastas is to d is tan t s ite s . T he variou s TNMsub se ts th us c lassified are then g rouped in to a sm all num berofs tag es ofd isease so tha t p a tien ts in each stage group have asim ilar life ex pec tancy .Focus o fP rob lem Areas

T o presen t the new in te rna tiona l stag ing p rop osa l in am ean in gfu l con tex t, I w ou ld lik e to d iscuss the p rob lem s w ithpresen t sys tem s and som e o f th e d ata used to proposeso lu tions . I co llec ted and stud ied varia tions in the use of th eTNM sys tem tha t h av e been repo rted in the lite ra tu re andexpressed in lette rs and recomm end ation s o fvarious grou ps8From the D epartm en t o fT horac ic S urgery , T he U niversity o f T exasSys tem Cance r C ente r, M . D . A nd erson H ospita l an d Tum o rInst itu te , H ouston .This p ro jec t w as sup po rted b y the fo llow in g organ iza tio n , fo un da-tion s, p r iv ate don ors , and g overnm ent agenc ies : Am er ican Jo in tC omm ittee on C ancer, H awn Found a tion of T ex as, H erm an N eelH ipp Fund for R esearch in T horac ic S urg ery , K e lsey -S eybo ldF ounda tion gran t 996 , N a tio nal C ance r Ins titu te D iv isio n of C ancerT rea tm en t (con trac t C A 34503 R eferen ce C en te r fo r A n atom ic andPatho log ic C lass ific ation o fL ung C an cer o fth e L ung Cance r S tu dyG roup), P riva te D onors F und fo r R esearch in T horacic S urg ery ,(D epartm en t o f T horac ic Su rgery , U nivers ity o f T exas S ys temCancer C en te r M . D . A nderso n H osp ital).

R ep rin t reques ts: D r M oun ta in , U n ivers ity o frexas M . D . A ndersonH osp ita l, H o uston 77030

of trea tm en t spec ialis ts . A new data b ase of con tem porarycase record s of lung cancer pa tien ts w as assem b led toexam in e som e ofthe questio ns ra ised by the v a ria tions stud y .

Methods: The da ta base fo r th e c lass ifica tion re sea rchpro jec t co nsis ted of3 ,7 53 pa tien t records and is desc ribed inT ab le 1 . A ll pa tien ts w ere a t risk a t least 24 m on th s, andfo llow -up w as com ple te th rou gh D ecem ber 1 984 . S urv iva lcu rv es w ere genera ted acco rd ing to the m eth od o f G ehan .& SZ ero tim e w as the da te o f f irs t trea tm en t. O pe ra tive death sare exc lud ed . T he term in al even t is dea th from cancer o runknow n cause .

S tag e G roup in g: A num ber o fen d-re su lts rep o rts su ggesttha t the p resen t stage g roup ing of TNM subse ts inc lud esw ide va ria tion in su rv iv al cha rac ter is tic s . ' T he end resu ltsfo r pa tien ts w ith T i NO M O tum ors-70-85% expec ted tosu rv ive 5 years -have prom pted m any to ques tio n wheth ersu ch tum ors sh ou ld b e assigned to a sep ara te s tag e gro up .O ne of the m a jo r d iffe rences in the tw o m os t w ide ly useds tag in g sys tem s is the ass ignm ent o f T i N i tum ors . T h eexperience o f the Japanese C ancer C omm ittee , w h ichrepresen ts a ca re fu lly c lass if ied da ta b ase , sugges ts th at th eou tcom e for pa tien ts w ith T i N i tum ors m ore clo se ly resem -b les the su rv iva l p atte rn ofp atien ts w ith stage II lun g cancerthan tha t o fthe o th er s tage I subse ts . T he surg ica l onco log is tshave iden tified specific g roup s of pa tien ts w ith stage Ill-M Odisease w ho h av e a su perio r p rog nos is com pared w ith th osewith stage Ill-M O tum ors th at a re no t operab le .

I t is comm on am ong treatm en t sp ec ia lis ts to sub d iv id es tag e II I d isease in to lim ited o r ex tensive ca tegories , bu tthe re a re no tab le incons is tenc ies in th e use of th ese te rm s .The n eed fo r g rea te r sp ec if icity fo r th ese g ro ups o f pa tien tsha s been em phasized , p articu la rly b y m ed ica l on co log iststrea tin g p a tien ts w ith und iffe ren tia ted sm all ce ll lung can-cer . 6

The p re sen t U ICC stag ing recom m enda tio ns design ate all

Tab le 1-New Stage D ata B asefo r C lasss fica tion R esea rch1975-82

Un iversity ofTex as M . D .A nderson H osp ita l* 2 ,749

Re ferenc e C en ter fo r A na tom icand P atho log ic C la ssifica tio nof L ung C an cer t 1 ,004To ta l cases 3 ,753

8C on secu tjv e p atien ts trea ted for prim a ry lun g can cer 1 975 -80 ;su rg ical p atien ts o n ly 1 981-8 2 .

tPa tie n ts treate d for pr im ary lu ng cance r by the N a tion al C an cerIn stitu te coo perativ e L ung C an cer S tud y G ro up-rep resen ta tiv es lide m ate ria l and case d ocum enta tion su bm itted to th e R efe renceC en te r fo r A na tom ic an d P a th o log ic C lass if ica tion o f Lung C an cerf o r c o nf ir m a ti o n of stag ing and histo log y 1977-82 .

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226S IV W orld C on fe rence on Lun g Cancer

d istan t m etas tas is as sta ge IV , w h erea s in th e A JCC recom -m enda tions , pa tien ts w ith M i d isease a re c lass ified as stageIII . T h ere is n o p ro b lem w ith m od ify ing the A JCC ru le s toinc lude a s tag e IV classifica tio n fo r a ll d istan t m etas ta ticd isea se; how ever , the q ues tio n o fw hether to as sig n p atien tsw ith sup rac lav icu lar or sc alen e lym ph nod e m eta sta sis to as tag e III o r stage IV group rem ains to be answ ered .

O ur sta rting po in t fo r exam in ing th e qu es tions regard ingstage gro up ing w as to exam in e the su rv iva l charac te ristic s o feach TNM subse t c lass ified accord ing to presen t recomm en -da tions of the A JCC for clin ica l and surg ica l s tag ing and torev iew th e d iffe rences o vera ll and fo r each ce ll typ e. T hecum ula tive prop ortion o f p atien ts expec ted to su rv ive 5years and the m ed ian surv iva l tim e fo r each ofthe c lin ica l an dsu rg ical TNM subse ts a re show n in T ab le 2 . Th e ordering ofthe en d resu lts and sim ila ritie s and sta tis tica lly s ign ifican td iffe rences in ou tcom e be tw een the subse ts ind ica te tha t anum ber of stage grou p ings are ra tion al fo r com bin ing pa-tien ts w ith sim ila r p rogno ses . T he presen t recomm enda tio nsstill w ork very w ell fo r iden tify ing 3 or 4 s tag e gro ups , eachw ith a un ique surv iva l pa ttern . T h ere a re severa l o the r w ays7th at the TNM subse ts can b e com bined tha t w ill p rov id e 3 , 4 ,o r even 5 s tages ofd isease w ith s ign ifican tly d iffe ren t su rv iv a lra tes ; how ever, these proposa ls m ake no a ttem pt to m ee t theneeds of trea tm en t sp ecia lists fo r s tag ing tha t is cons isten tw ith co n tem pora ry trea tm en t p lann ing as w ell as fo r es tim at-in g p ro gn os is .TN M D escr ip to rs

W e found tha t cla ssif icatio n prob lem s w ith the TNMcatego rie s w ere rela te d to the T 3 de scrip to r fo r ex tra pu lm on-ary , bu t in tra th ora cic , p rim ary tum ors; to the N 2 descrip to rfo r m ed ias tina l lym ph node m etastasis , and to the M ldesc rip to r fo r d istan t m etas tasis.

T 3 D e sc ri pto r: The curren t de fin ition fo r T3 is a tum or o fany siz e w ith d irec t e x te nsion in to an ad jac en t structu re suchas th e p arie ta l p le ura o r ches t w all , the d iaphragm , o r them ed ias tin um and its con ten ts; o r a tum or d em ons trab lebro nch oscop ical ly to in vo lve a m ain bro nch us les s than 2 .0cm d ista l to th e car ina ; o r any tum o r as so ciated w ith a tele c-ta s is o r ob struc tive pn eum onitis o f an en tire lun g or p leu ra lef fusion . T h is defin ition encom passes a b road spec trum of

Tab le 2-N ew S tage D ata B ase -C um ula tive P ercen ta geSurv iv ing F ive Y ears a nd M ed ian Surviva l by C lin ica l

and Su rg ica l TNM Subse tsClin ica l Surg ica l

M ed ian M edianTN M % Surv iva l, % Surv iva l ,Subse t N o . Surv iv ing m o . N o. Surv iv ing m o .

T i NO M O 591 61 .9 6 0+ 429 68 .5 60+T2 NO MO 1,012 35.8 2 6 436 59.0 60+T i N i M O i9 33.6 20 67 54 .1 60 +T2 Ni MO 176 22.7 i7 25 0 40 .0 29T3 NO MO 221 7.6 8 57 44 .2 26T3 Ni MO 7i 7. 7 8 29 17 .6 i6A ny N2 M O 497 4 .9 ii 16 8 28 .8 22A ny M i i,i66 i .7 6 - - -

Total 3 ,753 1,436

p rim ary tum ors w ith vary in g deg ree s of ex trapu lm ona ryex tens ion .

T h e c lin ica l s tag ing system for lu ng cancer p roposed by theR ad ia tion Therapy O nco log y G ro up (RTOG ) in the U nitedS ta tes (p erso na l com munic atio n , G . S eyd el, A p ril 19 85)prov ides fo r separa tion o f lung tum ors w ith ex trapu lm onaryex tens io n in to tw o ca tegories -one fo r w hom loca l con tro l byrad iat ion therapy is fe asib le and ano the r w ith ex tensivein tra th orac ic sp read in w hom pallia tion is the o n ly trea tm en tob jec tive . T hese ca tegories a re fu rthe r subd iv id ed by theROTG in to spec ific subsets o fpa tien ts accord ing to techn ica lfac to rs o f trea tm en t p lann ing .

T h e surg ica l onco log is ts h av e iden tified pa tien ts w ith T 3tum o rs w ho are cand ida tes fo r com ple te resec tion and thushave th e poten t ia l fo r an im proved surv iva l com pared w ithin ope rab le patien ts in th is cate go ry . T hese tum o rs are (1 )periphera l tum ors inv ad ing the chest w a ll, (2 ) tum o rs w ithd irec t ex tens ion to in vo lve the m ed iastinum or p er ica rd ium ,(3) sup erio r su lcus tum o rs in pa tien ts w ith no true P ancoas tssyn drom e, and (4 ) tum ors in vo lv ing th e prox im al m ainbron chus and carina tha t a re am enab le to tracheobro nch ial o rsleeve

N 2 D escrip to r : M edias tina l lym ph nod e m etas tas is,w he ther ipsila te ral o r con tra la te ral , is c lass ifie d N 2 in p res -en t system s. W ith in th is N 2 g rou p , sele cte d pa tien ts w ithmetastasis lim ited to th e ipsila te ra l m ed iastina l lym ph nodesmay undergo com ple te resec tion . A far be tter ou tcom e isan ticipa ted fo r such pa tien ts than fo r th ose w ith m oreex tensive m ed ias tina l m etastasis, w h ich obv ia tes con side ra -tion fo r su rg ica l trea tm en t.

M l D esc rip to r: The su prac lav icu la r and con tra late ra l h ila rlym ph node s are cla ssified as M l d isease in cur ren t recom -m enda tio ns. Th ese lym ph nod es a re usual ly in clu ded in th efield o f irrad ia tio n trea tm en t. T h ey are co nside red reg io na lby the rad ia tion onco log is t and are no t ap proached by themin th e sam e m anner as d issem ina ted T he prog nosesfo r pa tien ts w ith con tra la te ra l m ed ias tina l lym ph node in -volvem en t fall w ith th is g rou p . T he con trala teral m ediast inallym ph nodes are inc luded in the reg ion al trea tm en t fie ld o frad io th erapy w ith th e contrala tera l h ilum and supraclav icu-lax no des , so th ere is sou nd lo g ic fo r ass ign ing al l o f the segroup s to an N 3 designa tion .

THE NEW INTER NAT IONAL STAG ING SY STEMFO R LUNG CANCER

W e have derived a new nom enc la tu re fo r s tag ing lun gcancer tha t re ta ins the va lid an d usefu l com ponen ts o fcurren t system s and has n ew elem ents to m eet the ne ed s oftrea tm en t spec ialis ts fo r classifica tion re la ting to th erap eu ticop tio ns-as w ell as fo r es tim ating p rogno sis .

In terna tiona l A greem en tM em bers o f th e T ask Force o n th e L ung ofT he A JC C m ade

the ir eva lua tio n ofm y da ta and recomm enda tions , a long w iththe ir ow n end resu lts and th e end resu lts o f o thers ,# {176 } andthe prop osa ls m ade by the in te rn ation alTNM stu dy comm it-tees of th e U ICC w ith spec ific recomm enda tio ns from Japanand G erm any . T h is g roup then m ade recomm enda tions fo rm odifica tion ofthe A JC C stag ing system forlung cancer to b econ sis ten t w ith in te rn a tion al ob jec tiv es (see append ix ). T he


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Tab le 3 -TNM Def in i t ions Tab l e 5 -TNM Defin itions

CHEST I 89 I 4 I APR IL , 1986 I Supp lemen t 227S

P rim ary Tum or (T )TX Tum o r pro ven by the pre sen ce of m alig nan t cells in bro nch o-

pu lm ona ry secretio ns b u t no t v isua lized ro en tgen ograph ica llyor b ro nch oscopical ly , o r an y tum or that cann ot be a sse ssed as ina re trea tm en t s tag ing .

TO N o evid enc e of p rim ary tum or.T IS Ca rcinom a in s ituT i A tum or tha t is 3 .0 cm or les s in gre ate st d im ension , sur rou nded

by lun g or v isce ral p leu ra , an d w ith ou t ev idence of inv asio npro x im al to a loba r b ro nch us at bro nchoscop y .

T2 A tum or m o re than 3 .0 cm in grea tes t d im ens ion , o r a tum or ofany s ize that either inv ad es the v isce ral p le ura o r ha s associa teda te lec tas is o r ob struc tive p neum onitis ex tend ing to th e h ila rreg ion . A t b ro nchosco py , th e prox im al ex ten t o f dem ons trab letum or m us t be w ith in a lo bar b ron ch us o r at le ast 2 .0 cm dista lto the car ina . A ny a sso cia ted atelec tas is or obs tru ctiv e pn eu-m on itis m u st inv o lv e less th an an en tire lun g .

T3 A tum or of any size w ith d irec t ex te ns ion in to th e che st w a ll( in clu d in g su per io r su lcus tum ors ), d iaph ragm , o r the m edi-a stinal p le ura o r pe rica rd ium w itho ut invo lv ing the h ear t, g reatvesse ls , trachea , esophagus or verteb ra l bo dy , o r a tum or in th em ain bro nchus w ith in 2 cm of th e c arin a w itho u t in vo lv in g thecar ina.

T4 A tum or of any s ize w ith invasion of the m ed iastinum orinvo lv ing hea rt, g re at ve sse ls, trachea , esoph agu s, v ertebralb od y or car ina or p resenc e of m a lig nan t p leu ral e ffus ion .

* See T ab le 6

U IC C group s m ad e the ir recom m enda tion s fo r m od if icatio nof tha t nom enc la tu re , and the p roposa l show n in T ab les 3 -7w as agreed on by a ll o fthe in te rna tiona l rep resen ta tives (seeappend ix ) .TN M D efin itions

The new defin itions fo r the TNM catego ries a re show n inT ab les 3 -6 , and se lected new elem en ts a re illu s tra ted inF ig ures 1 -6 .

T -P r irnary T um o r: The descrip to rs fo r th e pr im ary tum orp rov ide fo r c lass ifica tion o f 4 d is tin c t leve ls o f tum or pro -g ress ion th at h ave d iffe ren t im p lica tio ns fo r tre atm en t S e-lec tion and p rogno sis, dep en d ing o n th e s tatus o fthe reg ion allym ph nodes and the presence or absen ce ofd is tan t m etas ta -s is . T he Ti des ig na tion is assigned to th ose sm all tum ors w ithno invas io n pro x im al to a lob ar b ron ch us and no invo lvem en to f the p leu ra . T o a id in th e c lass ifica tion of the uncomm onsu perfic ia l tum or w ith the in vasive com pon en t lim ited to th ebro nch ia l w a ll, w h ich m ay spread alon g the m ain b ronchus ,the fo o tno te show n in T ab le 6 has been add ed to th edefin itions . T he T2 c lass if ica tion is assign ed to tum ors la rgerthan 3 cm or th ose invo lv in g th e v isce ra l p leu ra or m ainbro nchus , reg ard less o f size , and th ose w ith a te lec tas is o r

- Tab le 4 -TNM Defin ition sNoda l Invo lvemen t (N )NO N o dem onstrab le m etastas is to reg io na l lym ph nodes .N i M eta stas is to lym ph node s in the pe rib ron ch ial o r the ip sila teral

h ilar reg ion , or bo th , in clu d in g d ire ct ex ten sio n .N2 M etas tas is to ips ila te ra l m ed ias tin a l lym ph nodes and subcarina l

lym ph nodes.N3 M eta stas is to co n trala tera l m ed iast ina l lym ph nodes , con -

tra la tera l h ilar lym ph nodes , ip sila teral o r co n trala tera l sc ale neo r sup rac lav icu lar lym ph nodes .

D ista nt M eta stas is (M )M O N o (know n) d istan t m etas tasisM i D ista n t m etastasis presen t-S pecify S ite(s)

obstruc tive pneum onitis ex tend in g to th e h ila r reg ion . T u -m ors w ith lim ite d , c ircum sc rib ed , e x trapu lm ona ry ex ten-s io n inv o lv ing th e chest w a ll, the prox im al m ain bronchus ,m ed iastina l p leu ra or p er ica rd ium are assigned to the T3ca tegory (F ig 1). Inc luded are tum ors o rig ina ting in thesuperio r su lcu s tha t have no accom pany ing Pancoas ts syn-d rom e o r invas ion of the verteb ra l b ody (F ig 2). T4 def inesth ose tum o rs w ith ex ten siv e ex trapu lm ona ry ex ten sio n in -vo lv ing the m ed iastinum , m ajo r vesse ls , n erves, or , in thecase ofP ancoas ts tum ors , the v er teb ral b ody (F ig 3 an d 4 ). T oa id in the c lassifica tio n o fp leu ra l e ffusion a foo tn o te has beenadd ed to th e defin itio ns regard in g the im plica tions o f p leu ra lflu id as a stag ing e lem en t. P leu ral e ffus ion in pa tien ts w ithlu ng cance r is usually re la te d to the m align ancy and is a po orpro gnos tic s ig n ; how ever, in a few p atien ts cy topa tho log icexam ina tio n ofp leu ra l flu id -on m ore th an on e spec im en-is neg ativ e for tum o r, is non blo ody , and is no t an exu date . Ifthese e lem en ts and c lin ica l judgm ent d ic ta te tha t the e ffu -s io n is no t re la ted to the tum or, the p atien t shou ld be s tag edT i, T 2 , o r T 3 , exc lu d ing effusion as a stag ing e lem en t. P a-tien ts w ith m align an t p leu ra l e ffus ion , as de te rm ined d in -ically o r from cy to log ic exam ina tion of th e flu id , a re c lass ifiedas T4 .

N -R eg iona l Lym ph N od es: In vo lvem en t o f the in -tra pu lm ona ry lym ph nodes by direct ex te ns ion o r m etastasisis c las sified as N i. M eta sta sis to th e ip sila te ra l m ed ias tin allym ph node s and subcarin al n od es is des ign ated N2 in thenew def in itions (F ig 5). M etastasis to the co n tra la te ra lm ed iastina l nod es, co n tra la te ra l h ilum , or ip sila te ra l andcon trala te ra l suprac lav icu lar o r sca lene lym ph nod es is c lass i-fled as N3 (F ig 6). A lthough the prognosis fo r p a tien ts w ithsu pra cla v icu lar lym ph nod e m eta stas is w as no t fou nd to b em a rked ly sup erio r to those w ith o the r M i d ise ase , pa r-ticu la rly tha t o fs in g le site s, the N 3 designa tion is ra tion a l fo rtreatm en t p lan n ing . A lso , th is design a tion prov ides fo r sepa-ra te s tage g roup in gs fo r pa tien ts w ith lim ited and ex ten -siv e d is ea se .

M -D istan t M e tas ta sis: The d es igna tion fo r d issem ina tionof tum or to d is tan t m eta sta tic site s is M i.S tage G rou p ing

S tage gro up ing of the TNM subse ts is sh ow n in T ab le 7.Tab le 6-TNM Defin ition sFootno te to TN M Defin itions

T i* Th e uncomm on su per fic ia l tum or o fan y siz e w ith its in va sivecom ponen t lim ited to the b ro nch ial w a ll w hich m ay ex ten dprox im al to the m ain bronchu s is c lassified as T i.

T 48 M ost p leu ra l e ffusion s asso cia ted w ith lung cancer a re d ue totum or. T he re are , how ev er, som e few patien ts in w hom cyto -path o log ical ex am ina tion of p leu ral flu id (on m ore than on espe cim en) is n ega tive fo r tum or , the flu id is n on -b lood y and isn o t an ex uda te . In such ca ses w he re the se elem ents and cl in ic alju dgm en t d icta te tha t the effu sio n is n o t re la ted to the tum or,the p atie n ts sho uld be staged T i , T2 or T3 , ex clu d in g e ffus ion asa s tag ing elem ent.


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F IGURE 2 . T 3 : S up erio r su lcus tum o rw ith n o in vo lvem en t o f th e verteb ra lbody .

228S IV W orld C on ference on Lung Cancer

T3A tum or o f any s ize w ithd irec t ex ten s io n in to the (a )che s t waD (b ) ( includingsupe rio r su lcus tum o rs),d iaph ragm or them ed ia stin a l p le u ra o rpe rica rd ium , w ith ou tinvo lv in g the hea rt, g re a tvesse ls , trachea , e sophaguso r ve rte b ra l b ody , o r atum or in the m a in b ronchusw ith in 2 cm . o f the ca rinaw ithou t invo lv ing theca r ina .

F IGURE 1 . T 3: A tum o r of any size w ith d i-re ct ex ten sio n in to the (a ) ches t w a ll (b )in clu d in g su per io r su lcus tum ors .

T he new in te rn atio na l p rop osa l fo r stag ing exc lud es tum orsw ith lym ph nod e m e ta sta sis from stag e I d isease (F ig 7). T hede le ter iou s e ffec t on prognosis o flym ph nod e m e tasta sis h asbeen show n in m any stu d ie s , such as those o f the JapaneseC ance r C om mittee s an d the S loan -K ette rin g C ance r C en -te r. In ou r ow n s tud ie s , in trapu lm on a ry m e ta sta sis w aspa rtic u la rly u nfavo rab le in pa tien ts w ith aden ocarcinom a.

S ta ge II lun g can ce r inc ludes a ll p atien ts w ith T i and T 2tum ors w ith m e ta sta sis to the pe rib ronch ia l, loba r , and h ilarlym ph nodes, inc lud ing th ose in vo lv ed by d irec t ex ten sion .Th e new stage grou p ing ru le s spec ify the T i N i and T 2 N isu bse ts a s s ta ge I I d isease (F ig 8).

S ta ge III d isease is subd iv ided in to s tage lila an d IlIbc ate gor ies . Pa tien ts w ith T 3 NO or N i d isea se and those w ithT i-3 p rim ary tum ors w ith m e tasta sis lim ited to the ip silate ralm ed iastin a l an d subca rin al lym ph nodes a re c las sified ashav ing stag e lila d isease (F ig 9 ) . Th e new stag ing nom en-c la tu re spec if ie s th at stag e Ilib d isease inc lude pa tien ts w ith

Esophagu sT ra chea

ex tensive ex trapu lm onary tum ors, T 4 , tha t h av e no d is tan tm etas tasis. P atien ts w ith m etastas is to th e con trala te ra lm ediastina l and h ila r n odes o r the sup rac lav icu la r o r sca len elym ph nodes , w he th er ips ilate ra l o r con tra la te ra l, o r bo th arec lass ified as hav ing stag e IlIb d isease . T h is stage groupinc ludes pa tien ts w ith the T 4 com ponen t and any N value orw ith an N 3 com ponen t an d any T va lue (F ig 1 0). P atien tsc lass ified as hav ing stage lila or stage Ilib d isease have nod istan t m etastas is . O n ly pa tien ts w ith d istan t m etastas is a reclassified stag e 1V .E nd R esu lts Accord ing to th e N ew S tag ing Propo sa l

W hen th e TNM defin itions and stage g rou p ing ru le s a reap p lied to a la rg e con tem pora ry da ta b ase, th e end resu ltsshow n in F ig II a re o b ta ined . T hese su rv iva l pa tte rn s a rede rived from c lin ical e stim a tes o fd is ea se ex ten t. E ach s tag ehas a un ique surv iva l ex perience an d re lationsh ip to trea t-m en t p lann ing . Pa tien ts w ith c lin ica l s tag e I, II, o r lila non -

Lung (apex o f upper lobe )

R ib R ib II (he ad an d th o rac ic gan g lion )T ho ra c ic v er teb ra II (sp ino us T ho rac ic v erteb ra I

T3 A tum or o f a ny s ize w ith d irec t ex tens ion in to th e chest w a ll( inc lud ing superio r su lcus tum o rs). . . .w ithou t invo lv in g th ev er te br al b od y.


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Tab l e 7-S tage G ro up ing o f TNM SubsetsStage G rou ping

TX NO

T4

II (he ad and tho rac ic g ang Iio n

CHEST I 89 I 4 1 APR IL , 19 86 1 Supp lemen t 229S

O cc ult C arc in om aStage 0 115 C arc inom a in situS tag e I T i

T2NONO

M OM O

S tag e I I T iT2

N iN i

MOMO

S tag e lila T 3T3T1 - 3

N ON iN 2

M OM OM O

S tage I lib A ny TT4

N 3AnyN

M OMO

S tag e IV A ny T A ny N M i

sm all ce ll lung cancer usua lly are can d ida tes fo r defin itivesu rg ica l trea tm en t, and those w ith stage IlIb and s tage IVd isease a re gene rally a ssign ed to rad io th erapy , chem oth er-Super io r V ena C ava

Syndro r , e e

ap y , o r com bined m oda litie s . C hem otherapy or com b in ed= pro gram s are usua lly the trea tm en t o fch o ice fo r pa tien ts w ith

u nd iffe ren tia ted sm all ce ll ca rc inom a, regard less o f s tage ;M O howev er, the p ropor tion of pa tien ts ex pec ted to ach ieve the

com p le te respon se necessa ry fo r long -term surv iv al variesw ith the s tage ofd isease . T he trea tm en t reg im en is re lated tothe s tage c lass ification ofsm allce ll tum orsjus t as it is fo r stageIIIb o r IV non -sm all ce ll lun g can cer .

CONCLUS IONThe new in te rn atio na l p ropo sa l fo r stag in g lun g can cer has

five s tag es ofd isease , in c lu d ing a S tag e 0 , tha t p rov ide fo r thec lass if ica tion of six grou ps of pa tien ts w ho have sim ila rp ro gnos tic expec tation s and therapeu tic o p tio ns. S tage Iinc ludes on ly p atien ts w ith th e best p rogn ostic exp ecta -tio ns-tho se w ith T i o r T 2 tum ors and no ev iden ce ofmetas tas is . S tage II d isease inc ludes those pa tien ts w ith aprim ary tum o r c lass ifica tion ofT l o r T 2 and m etas tas is to th ein trapu lm onary (in clud in g h ila r) lym ph nodes. S ta ge Illa

A tum or o f a ny s ize w ithinvas ion o f them ed ias tinum , o r invo lv in gheart , grea t vesse ls ,tra chea , esophagus,ve rteb ra l b ody o r ca rina o rp resence o f m a lig nan tp leu ra l e ffus ion .

F IGURE 3 . T 4 : S up er io r vena cav a syn-drom e -tum o r inv o lv ing gre at ve sse ls.

T4 A tum or o f a ny s ize w ith in vas io n o f the ve rte b ra l body(un resectab le - tru e Pancoas ts S ynd rom e ). F IGURE 4 . T 4 : T um or inv ad ing the ver -teb ra l bod y-unresectab le , p roducesP an co as ts sy nd ro me.


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N 3In vo lvem en t o f co n tra la te ra lo r i ps il at er alsuprac lav icu lar/sca lenelym ph nodes.

N 3

T2 NO MO -

Invo lv ingv isce ra l p le ura

Per iphe ra l co in les ion

S tage INo Lym ph N ode In vo lv em en t

N 2-

230S IV W orld C on fe rence on Lung Cancer

F IGURE 5 . N 2: In vo lvem en t o f ips ila te ra lm ed ias tin a l and /o r subcarina l lym phnodes .

F IGURE 6 . N 3 : Invo lvem en t o f co n-tra late ra l o r ip sila te ra l sca lene or su -p rac lav icu lar lym ph nodes; con tra late ra lmediast inal or co n tra la te ra l h ila r lym phnodes .

F IGURE 7 . S tage I d isease .

Invo lvem en t o f ip s ila te ra lm ed ias tin a l and /o rsubca rina l lym ph nodes

N2


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T3 NO MOS up erio r su lcu st umor -

CHEST I 89 I 4 I APR IL , 1986 I Supp lemen t 231S

T2 N i M OInvo lv in g m ain-b ron chus and h ila rlym ph node s

F IGURE 8. S tage I I d isea se .

T3 N i M OP erip he ra l tum or-in vo lv ing chestw all a n d in tra -p u lmona r ylym ph node s

F IGURE 9 . S tage l ila d is ease .

T4N3MO

I Mediastinalpa rie ta l p leu raS tage Ill-b

In vo lvem en t o f m ed ia s tin um ,

L - ip s ila te ra l a n d ) co n tra la te ra lm ed ia s tin a l lym ph nodes ,contra la te ra l h ila r n od es ,sup ra c la v icu la r lym phnodes

F IGURE 10 . S tag e Ilib d isea se .


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p < .001)C>>U )C0t00.0a)>CD

E0

100

80

60

40

20

0

. %

\ \ \% \ \

% \ S ta ge lila\\ \\ = 261)\ \, Stage I lIb

\%%% N = 543 )Stage IV (N=635)

R ev iew ed R eco mm end ations :H erbert D erm an , M .D .W illis J. Tay lo r, M .D .

Stage Il(N = 169)U IC C R ep re se nta ti ve s:

L es lie So bin , M .D .A rno ld Lev in e, M .D .

G erm an TNM Comm ittee :W alte rC . R e iner, M .D .Pau l H e rm anek , M .D .

Japanese TNM Com mittee :H eizab uro Ich ikaw a , M .D .

A JC C R ep re se nt ati ve s:H arv ey B ak er, M.D . ,C ha irm an A JCC

David Bragg , M.D .Rob ert V . P Hutter, M.D.B. J.Ken nedy, M. D.C lif to n F M ountain , M .D .E llio t S trong , M .D .Mad e l y n A . M urray , sta ff

232S IV W orld C on fe rence on Lun g Cancer

12 24 36 48 60M on ths Fo llow ing T rea tm en t

CFMo,7 tas ; 7 9 9 5F IGURE II . C um ula tiv e p ro por tion o f pa tien ts surv iv ing 5 y ears byclin ica l sta ge of d ise ase .

d isease d es igna tes th ose pa tien ts , usu a lly w ith in th e rea lm o fthe su rg ica l onco log ist, w ith ex trap u lm ona ry ex ten sion o f thep rim ary tum or and /o r ip sila tera l m ed ias tina l lym ph nod emetas tas is . S tage IJIb in clu des p atien ts w ith m ore ex tensiv eex trapu lm on a ry in vo lv em en t th an in the p o ten tia lly op erab legrou p , th ose hav ing m alignan t p leu ra l e ffusion an d thosew ith m e tas tasis to the con tra la te ra l m ed ia stinum , h ilum , o rsup rac lav icu lar and sca len e lym ph nodes . S ta ge IV d isease isre se rv ed fo r p a tien ts w ith m e tas tasis to d istan t site s .

T hese new recomm enda tions fo r stag in g fill th e need fo rspec ific defin itions fo r lim ited and ex ten sive d isease tha tcan be rep ro du ced an d com pared . F urthe r , they m ee t thegoa l o f m od ify ing pre sen t c la ssif ica tion s to p rov ide a un iv er-sa l, s ing le s tag ing sys tem for lu ng can cer tha t is respo nsive tothe needs ofa ll tho se inv o lved in the trea tm en t an d study o flu ng cancer.

APPEND IXM eeting fo r U nifica tion of S tag ing D efin itions

H aw aii, D ecem ber 6-7 , i9 85U IC C R ep re se nt at iv es :Leslie S obin , M .D .,

Chairm an , TXM Comm itteeA rno ld Lev in e, M .D .

J apanese C an cer C om mitteeH eizab uro Ich ikaw a , M .D .,

H ead of de leg ationTo sh ifum i l izuk a, M .D .Take sh i Iw ang a, M.D .K eiich i M a ruy am a, M .D .M asak azu M aruy am a, M .D .K iyosh i M iw a , M .D .

T su guo N a ruk e, M .D .M itsum asa N ish i, M .D .Y uk ioO hm on , M .D .Isam u O no, M .D .S unich i Sakai , M .D .

Am erican Jo in t C omm ittee T ask Force on LungS tag ing Rev ision M ee ting -H ous ton , Tex as, M arch 30 , i9 85

C lifton F M ountain , M . D . , ChairmanDavidT Car r, M.D.Nael Martini, M.D.F rederick P S titik , M .D .

U ICC A nnua l M ee ting -G eneva , A pril 2 0 , 1985R obert V . P H utte r, M . D . , tra nsm it ted recom m enda tio ns of th eAm erican Jo in t C omm ittee fo r con side ra tion of the U ICC .

F ina l L iaison M eeting-S to ckh olm , Ju ne 19 , i98 5A JC C R ep re se nt ati ve s:

H arvey B aker, M .D .R obert V . P . H u tte r, M .D .Clifton F M ountain, M.D .D onald E . H enson , M .D .

A CKNOW LEDGM ENT : Th e au thor w ishes to acknow ledge thesub sta n tia l co n tribu t ion s o f K ay E . H e rm es, Sen io r R esearchA ssis tan t, D epa rtm ent o f Thora cic Surgery , to the research andw riting of th is report, and of A nne M urphy , A ssis tan t E p idem i-o log is t, D epartm en t o fT ho racic Surgery , fo r da ta m anagem ent andprogramming .

R E FERENCESi Am eric an Jo in t Comm itte e on Cance r, T ask Fo rce on Lung .

S tag ing ofLung C ancer 1 97 9 . C hic ago : Am er ican Jo in t C omm it-tee on C ancer, i9 79

2 M ounta in CF . C arr DT, A nderson W AD . A sy stem fo r the c lin ica lstag ingo flu ngcan cer. A JR 1974 ; 120 :13 0-3 8

3 C arr D T , M ounta in CF The s tag ing oflung cancer. S em in Onco li97 4 ; 1 :22 9-3 4

4 H arm er EM . TNM C la ssif ica tion o fm alig nan t tum ors. G eneva :U n ion In te rna tion ale Con tre le C an cer , i97 8 :4 i-4 5

5 D enoix P F E nqu ete pe rm anent d ans le s cen tre s an tic anc ereux .Bu ll In st N at H yg 1946 ; i :70 -75

6 G ehan EA . S ta tist ica l m ethod s fo r surv iv al t im e stu d ie s. In :S taq ue t M J, ed . C ancer the rapy , p rogn ostic fac to rs an d crite ria o fre spo nse. N ew Y ork : R aven Press , 19 75:7-3 5

7 Sm ith T , Pu tnam JE , G ehan E . A com pu ter p rog ram fo r estim a t-ing surv iva l fu nc tio ns fo r th e life tab le . C om put P rog B iom ed1 97 0; 1 :5 8-6 4

8 L ee E , D esu M . A com pute r p ro gram for com paring K sam plesw ith righ t-censored da ta . C om put Prog B iom ed 1972 ; 2 :315 -21

9 M e lam ed MR . F leh ing er B J, Z am an M B , H eelan R T , Halle rmanET , M art in i N . D etection of true p ath o lo g ic sta ge I lung in ascre en ing p rog ram and the effe ct on su rv ival. C an cer 19 81 ; 47 :1182-87

10 W illiam s D E , P airo le ro PC , D av is CS , e t al. S urv iv al o f pa tien tssu rg ica lly trea ted fo r stage I lu ng cancer. J T horac C ard iov ascS urg 1981 ; 82 :70-7 6

ii M oun ta in CF , G ail MH . Su rg ica l ad juv an t in trap leu ral BCGt rea tm ent for stage I no n-sm all c ell lu ng can cer : p rel im inaryrep ort o f the N ationa l C ancer Ins titu te L ung C ancer S tu dyG roup . J T horac C ard iovasc S urg i9 81 ; 82 :64 9-5 7

12 Ish ik aw a S . S tag in g system on TNM cla ssif ica tion fo r lu ng cance r.Jpn J C lin O nco l 19 73 ; 6 :19-30


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CHES T / 89 / 4 / APR IL 1 986 / S upp lem en t 233S

13 G ilbert A , D es lau r ie rs J, M cLish A , P irau x M . T rachea l sleevepn eum onec tom y for ca rc inom a o f the prox im al left m ain bron -chus . C an J Surg 1 98 4; 2 7: 58 3-8 5

14 N aru ke T , Suem asu K , Ish ik aw a S . L ym ph node m app ing andcurab ility a t va rious leve ls o f m etas tas is in rese cte d lung cance r.J T ho ra c C ard iovasc Su rg 1978 ; 76 :832 -39

15 Pa tterson G A , live s R , G insb erg R J, Coop er JD , T odd TR J ,P earson FG . T h e va lue of ad ju van t rad io the rapy in pu lm onaryand ch es t w a ll r es ec ti on fo r b ro nchogen ic ca rc inom a. A nn ThoracSu rg 1 982 ; 34 :69 2-97

16 B unn PA Jr. C ohen M H , Ihde D C , F ossieck BE , M atthew s M J,M in na JD . A dvances in sm all ce ll b ro nchogen ic ca rc inom a.C omm en ta ry . C an cer T rea t R ep 1977 ; 6 1 :333-4 2

17 Yo shim u ra K . A clin ic al sta tis tica l s tud y oflung can cer pat ien ts inJapan w ith specia l re feren ce to th e stag ing system of TN Mclassif icat ion : a repor t from th e Jap an Jo in t C omm ittee o f L ungC ancer assoc ia ted w ith th e TN M sy ste m o f c lin ic al c la ssific atio n(U ICC ). R ad ia t M ed 19 83 ; 1 :18 6-9 5

18 M oun tain C F Th e b io lo g ic op erab ili ty o fstage III no n-sm all c elllu ng cancer. A nn Thorac Surg 1985 ; 40 :6 0-64

19 Cox JD . R ad io therapeu tic m anagem ent o f com plica tions o fca rc in om a ofth e lung . C lin C hest M ed 1982 ; 3 :415-2 0

20 P ieh le r JM , Pa iro le ro PC , W eiland LH , O ffo rd K P, P ay ne W P,B erna tz PE . B ronchog en ic carcinom a w ith chest w a ll in vasion :facto rs a ffec ting surv iva l fo llow ing en b loc resec tion . A nn ThoracS urg 1 985 ; 40 :60 -64

21 M artin i N , F leh inger B J, Zaman MB , B ea ttie E J J r. R esu lts o frese ctio n in no n-o at c ell carcin om a o f th e lu ng w ith m edia stin allym ph node m etas tases. A nn Su rg 1983; 198 :386-97

22 McCaugh an B C, M artin i N, Ban s M S. M cC orm ack PM . C hestw al l i nv as io n in carcin om a of the lung : therapeu tic and p rog-n ostic im plica tions . J T horac C ard iovasc S urg 1 98 5; 8 9:8 36 -4 1

23 M art in i N , F leh inge r B J, N agasak i F , H ar t B . P ro gn os tic sig nifi-can ce ofN i d isease in c arc inom a ofthe lu ng . J T ho ra c C ard io va scSurg 1 98 3; 8 6: 64 6-5 3

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