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Survival in Cancer of the Bronchus and Lung, 1949–1962: Comparison of Men and Women Patients
Surviva l in C an cer of thc Bron hus and Luna, 1949-1962 : Comparison of M en and , ,\ omen Patients ' V IL LI AM
L.
' VATS ON , · · "1.1l. ANIl
Dxvrn
S CII OTl"E:\FELO, " I.O : 'Hf
N ew Y ork, N ew Y ork
O
in untreated patients. from th e date th ey were first seen a t Memorial Center. The point s in time for computing rates of survival were set at mon thly intervals for th e initial six months and at three-mon thly intcrvals for th e subseq uent 54 months. When th e d ata permitted , the experiences of two coho rts of pati ents. 194 9-1 955 a nd 195()19() 2, were com pa red, A d j us t III c n twas made for sex and age differen ces in norm al mortality expecta tion by com puting relative su rvival rat es. T he relat ive sur viva l rat e is th e ra tio of the oh ervcd sur vival rate to th e su rviva l rat e expected in persons drawn from th e gene ral popul ati on at a com pa rahlc point in tim e with th e same cha rac teristics 1)\' race, sex and age as the pati ent group. 'T his adj ustme nt permit meaningful com pa rison of men and w om en patients a nd of patient grou ps tha t ma y d iffer with respect to age.' The standa rd error of the relati ve . u rv iva l rate was comput cd to esta blish confide nce limits and to pe rm it assessme nt of statistical significa nce of observed di fference .'
I NT RODU CT IO N
4000 I'AT IE l': T S WITI[ L U N G CANce r ha ve been see n a t th e M em ori al Ce nter for Ca nce r a nd Alli ed Diseases since 1930. Since 194 9. privat e a nd ward lu ng ca nc T cases ad m itted to th e M em ori al a nd J am es Ewin g Hospital s have been ente red int o th e Ca ncer R egistry a nd th e reco rds pro cessed by m ean s of pun ch ca rds a nd an electron ic co m pute r. I n addition , t he thora cic s '1"\' i c c has abstract ed clin ica l a nd pathologi c inf ormati on on all lung ca ncer cases treat ed sinc e 19 30 . The data deriv ed from th ese sou rces provid e th e m at erial for thi s r view of su rv ival a mo ng tre ated, as well as untrea ted ca ncer cases di agn osed during th e peri od 1949 to 1962 . VE R
M ETH OD O F A NALY SIS
The su rvival ra t wer e com pu ted b y th e life-table me tho d, whi ch permitted maxim um ut iliza tion o f a 11 ava ilable su rvival in forma tion lip to th e m ost I' 'cen t d at e of follow-u p in J a nua ry, 19() ().· Follow-up informati on was com plete for more th an 99 P ' I' ce nt of th e pati en ts. Su rviva l tim e was m easured from the d ate of tr eatment , or
R ES ULT S
.·lgc : The age distribution bv race a nd sex for pa tient s with ca rcinoma of th e lung a nd bronch us is s ho w n in T able I. T he fre-
* C h icf of Thoracic Servi ce . Em eri tus , M em orial C e nter for Cancer a nd Alli ed Dis eases. * * Di rect o r of Clinica l St a tisti cs, and Assistant D ir~ c to~. Admitt ing and Diagnostic Clinic. M emorial C. 'liter for C ance r an d All ied Di sea ses. TAIlI. E I -
A C E DI S TRllI lJ Tl O N II\" RA e \·: A :>;J) S EX POR P ATI E :>; T S W IT II C ARCI :>;O)\ ,\ O J' 1. 1' :>; ' : A N Il BRO :-:C:J1 U S , r- I DI OR IAI . CE:>;TE R ,
19·1 9- 1955. 1 9 5 6-1 91i ~
Non-whi te
Whit c 1949·1955
M en T o ta l Und er 45 45 -51 55-64 65 - 7·1
0"" "
75 a lii! M ed ian a ge
1328 81 340 526 3:15
(6) * ( 26 ) ('10 ) ( 25)
-I( ; (:ll
:\ v--ru ~'-' a~('
*(
Womcn
) Pe n "' utage age
59. 1 51l.:>
239 28 (1 2 ) 6'1 ( 27 ) 81 (3 4) 51 ( 2 1) 15 ( 6) 57 .9 5 7.5
Womcn
Men 130 7 78 ( 6) 288 (22) 55 1 (.l:!) 3:12 ( 25) 5/1 (-I ) 59.7 ':)9.1
250 33 78 69 56
( 13) ( 3 1) ( 28 ) (22 ) J.I ( 6) 56 .5 56.a
d istri hur io u lIlar not total 100 b vca usc
65
1956 -1962
19·19-1955
1956-1962
Mcn 42 3 ( 7) 16 ( 38) 14 ( 33) 7 ( 17) 2 (5) 55.9 56.5
or round ing.
Womcn 7 2 3
2
Men 43 2 16 17 8
( 5) (3 7) ( 39) ( 19 )
- (0 ) 56.6 56.:1
wome n 10 1 5 2
66
D isc .1SC S o f
WAT SON AN D S C H OTTE NFE LD 100 &l
MALES:
60
-
- - 1949- 1955
.'"
~
able at first h os p it al discharge, including that obta ined from exam ination of surgical specimens. L ocalize d ca ncer is con fine d to th e site of origin with out specifica tion as to the size a nd includes direct exte nsion with_ out metastases. R egion al c a n ce r includes clinical and / or microscopi c evidence of direct extension of d is e as e to neighboring organs, tissues or to region al lymph nod es. D istant ca ncer includes clinical and/or microscopic evidence of sprea d of disease to organ s or tissues beyon d th ose immedi ately d rain ing or bordering th e site of origin. The distribution of m en and women a t th e tim e of initial eva luation for th era p y as shown in T ab le 2 was not significantly different. At least 40 per cent of the cases demon strat ed d istant disease a nd th ere Was no indicati on of a ny relati ve increase ove r tim e in th e percen tage with locali zed ca n cer. The six-month, one-yea r, three-year a n d five-year relative survival rat es by stage o f disease for men and wom en without regard to treatm ent a re summa rized in Table 3 a nd Fig. I a nd 2. There was no significa n t improvem ent in t h e overa ll relative SUr_ vival rates for the men a nd wom en , a n d no essential d ifference between th e sexes . Am ong th e treated and u ntrea ted ea es with
Cases 1328
1956 - 1962 1301
FEM~I£~ 1949 - 1955
239
- - - - - 1956 - 1962
250
'"
~20
.
:::>
Vl
.~
0; 0:
10 8
I
o
2
I
I
3
4
Years aller Initial Treatment
I : Relative survi va l rates for white men and women with carcinoma of th c lun g and br onchus, all stages, 1949-1955 and 1956-1962, M em orial Cen ter. FIG U RE
qu ency distributions approximated normal curves and exhibited stability over time. Among the w hi te patients, the majority were with in the age int erval, 55 to 64 . S tage of Disease : The classification of pati ents by stage of disease was based on all information avail100
th e Ch e,t
Ma~ 1949- 1962
Fe~~:.s~ 1949- 1962
Cases 481
79
60
10
o
2
I
3
Years afte r Initial Treatment
I
4
5
F IG U RE 2 : Rela tive sur vival rat es for whi te men and women with ca rc inoma of the lun g and bronch us. localized d isease, 1949- 1962, Memoria l Center.
Volume H . 1"0. 1 ) , n u,ry, 1969
SU RVIVA L I • CANC E R O F BRON C HU S AND LUNG
'rAllLI, 2- D ISTRlIlUTI0:-; OF PATm :-;TS, \ \' Ill n : }.IE:-; A:-; 1l W O ~lE: :-; , WITII C A R C I:-;O ~ I A 01' L u x e A:-:1l BRO:-: ClI l' S Ae COIWI:-;C TO STAGE OF D ISI':ASE AT TDlI' 0 1' I:-: ITI.\ I. E \·AI.t ·ATIO:-; FOR TIII-:RAI'Y, ~ I E ~I O RI AI. C E:-;T ER . 19·19.1 955 A:-;1l 1956 · 1962 Stage of D iseas:A ll st ages Loca lized R egio n a l D i ~ l a nt
Unkn own
19 19-1955 Wom en M en Per Ce n t Number Per C ent N um ber 13 28 242 25 9 55 ,1 2 73
100.0 18 .2 19 .5 '11.7 20 .6
2:1:1 39 49 93 52
local ized disea se, th ere was a tw o- to th reefold increase in th e three- and five-yea r relative survival ra tes for both men a nd wom en . :\ mong th e m en with localized disease, th e six-mo nth and one-y ea r surv iva l rates were somewha t better th an a mo ng th e wom en , bu t th is ad va ntage was not .ubscq ucntly m a nifested .
II islology 0/ T um or : The d istri butions with in th e sex gro ups h y histologic type were st riking ly different (T a ble 1 ) , The histop athologic diagn oses were int erpret ed from biopsicd or surgically resected tissues in 90 per cent of instances a nd in th e r em ainin g 10 per cent from sp ut um , bron chi al washings or pleu ral fluid. .'\ m o ng th e design at ed cell types, ade noca rcinom a a nd termi nal bron chiolar ca rcinoma
100 .0 16.7 2 1.0 :19 .9 n :1
1956- 196 2 \Vom en M cn Number Per Ce n t Per Ce nt N um ber 130 7 239 25 3 60 3 2 12
250 40 57 110 ·13
100.0 18.3 19,4 46 . 1 16.2
100 .0 16.0 22.8
H .O 17.2
or hron chioloalveolar ca rcinoma (grou p 2 of Krcyhcrg ) formed a larger proporti on ( 25 per cent ) and were twice as common in th e wom en , while epidermoid a nd oat cell carcinoma (group I of K rcyberg ) predominated (53 per cent ) in the men . :\ d isturbingly large prop ort ion of tumors were un classified and anaplastic in both sex grou ps and th e minor shift in hi tology exhibited by th e 1956-196 2 cohor t of wom en reflected relative increases in adenocarcinoma and term inal bronchiolar ca rcinoma or bron chioloalvcolar carcinoma. H erm an and Crittenden" noted in th eir postmort em material th at ab out 30 per cent of tumor. were poorly differentiated carcinomas, "ith th e technique of differenti al sta ining for keratin and m u c in and th e classifica tion of cell type a d voc a t e d by
TAllL E 3- R I,I.ATI\·E S UR\,I\·AI. R ATES* FOR W IIITE 1'.11-::-; A:-; II \\' 0 ' 11-::-; WITII CAR CI :-;O~IA OF L u x e A:-:U BRONCII US IIY STAca : OF D ISI':ASE, 1 1r" I OJUAI. C E='TER, 19·19- 196 2 Local ized All Sta ges
Relat ive
R elative
Survi val
M en 0 -6 m onth s 0 - 1 year 0 -3 years 0 -5 years \Vo m en 0 -6 m ont hs 0 - 1 year 0- 3 yea rs 0 -5 years
Ratc
S.E.*
19'19-55 1956 .6 2 1949·55 1956-6 2 1949 ·55 1956-62 1949 ·5 5 1956 -6 2
32 .3 40 .8 18.4 22 . 1 6 .7 6 .2 5. 6 3.9
1.5 1.5 1.5 1.5 1.I 1.0 1.I 1.0
1949 -5 5 1956-6 2 1949-55 195 6-6 2 19'19-55 1956 -6 2 19 19 -55 1956 -6 2
35 .4 41.0 1U.7 20 . 1 6 .7 6 .9 '1..1
3.5 3.5 3.0 3.0 2.1 2 .0
.1.5
Su rvi val Rate
-
') _ .1
2.5
S .E .*
19,19-62
58.3
2.5
19·19-62
'12. 7
:!oS
1949-6 2
21.6
2.5
1949·62
17.0
3.0
1949-62
4 7.0
6. 0
1949 -62
3 1.0
6. 0
19-19·62
20 .:1
6 .0
19·19-62
17.9
a.n
* S u r \'i \'al rat es and stan d ard (' ITOrs o f rclar ivr- su rv iva l rat es a re expressed as pcrcc rua gcs.
WATSO N A ND S CHOTT ENF E L D
68
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or
I
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D iseases oi th e Chest
Kreybe rg," th ey reviewed th e u nd ifferen tiated sub-gro u p a n d observed subs ta n tial inc rease in th e adenoc arcino mas . For localized disease, the relative su rviva l rates in termin al bronc hiolar ( bronch ioloalveola r) carcinom a indi cat ed significa nt advant age for both men an d wom en with a grea ter sa lvage am ong th e latter (T able 5) . Previou s rep orts from Mem orial Ce nter hav e noted th at pat ien ts with termin al bron chiolar (bronchioloalveola r ) ca rcino ma had th e high est rat e of resecta bility a nd th e most favorabl e progn osis, while those with oat cell ca rcinom a dem onstrat ed the lowest favora ble rat e of rcscctabilirv and the least . .rva I .20 ·22 I n t he. pr esen t review, a pproxsu rv chi ola r bron l ina term of ima tely 2 1 per cent zed III locali as ed cell ca ncers were classifi were cent per 75 both sexes, a nd of th ese, th at d observe resected. H ukill an d Stern" p grou a as the bron chioloal veolar ca ncers difnot exhibited a varying course and did fer in prognosis from the ade noca rcinom as, a pa rt from those bron ch ioloalv colar tumors of unicen tr ic circum scribed origin th at w er e readil y resecte d. " The relati ve surviva l ra tes at three a nd five years of pat ients of h oth sexes with epide rm oid tumors were not significan tly differe nt. Although the pro portion of epidermoid tum ors classified as localized was com pa rable to tha t of the termin al b ron chiola r cell, the rat e of resecta bility for this group was 45 per cent in me n a nd 57 per cent in w om e n . In th e ade noc a rcino ma sub-grou p, th e limited numbe r of cases with localized disease did not permit meanin gful statistical com parison betw een men a nd wom en. In this review a nd within th e broad confide nce limit s of our data , th e relative surviva l rat es at th ree and five years for men with ad enocar cinoma , althoug h some wh at superio r, did not differ significantly from th e gro up wit h epide rmo id can cer. Among the men with ade nocarcinoma, th e proporti on with localized disease was 11 per cent, and of th ese, 40 per cent were resected . The Ca liforn ia Tumor Reg istry report ed that m en with localized adenoc arcinoma of the lung exhibited a less rapi d
Volume H . No .1 January. 1968
69
S U RV IVA l. I >: C ANC E R O F llRO " CIIU S A"D LUNG
TABLE 5- RELATIV E S URVIVAl. R ATES* I'OR \ \' 1I1T1: ~ I L. · A :" I> \ \' O:llf.. · WITII LOl:AI.IZEI, CARCI:-IO:lIA OF L U:-IC A:-ID BRO:"CII ' S llY I IISTOI.OI;(C T YI'E. ~h: :lI OR IA I. C E:"TER. 1 9 · 1 9 · 1 9 6 ~ R ela tive Surviva l R a te - - Loca lized D isease 11-:1 Years S.E. * l J.:j Yea rs S . I~ . * S .E . * 0· 1 Year H istologic Type All h istologic types M en W omen Epid ermoid ( sq u amous) M en W omen Terminal b ronc h iola r M en W o men Adenocarcinoma M en W om en
42.7 3 1.0
2.5 6 .0
2 1.6 20 .3
2.5 6.0
17.0 17.9
3.0 8.0
41.8 56 .3
3.6 7.3
22 .0 1-1 .1
3.6 6.0
13.9 1·1. 1
3.8 6. 0
68 .0 60 .1
7. 1 7.0
38 .-1 50. 1
7. 1 7.5
32. 9 45 . 1
8 .7 8.5
61. 2 **
7.2
:10.6
7.2
30 .6 **
8 .2
**
*Survival rates a nd sta ndard e rr ors a re ex p ressed as percenta ges. ** L ess th a n 10 ca ses.
rate o f cu m ulative mortality th a n those with e pid erm oid ca ncer: The d ata of th e Co nnecticu t Tumor Registry d id not ind ica te a nv consiste nt d ifference in th e su rv iva l rates for men and w om en by histologic types, alt ho ug h th e sq uam ous cell type offered a slightly poorer progn osis." These findings di ffered f r o m th ose of Co nnelly el al/ where th e five-yea r relative su rviva l rate fo r localized tumors in men was 41 per cen t for th e sq ua mo us cell type and 16 per cen t for th e a de noca rc i no ma gr ou p. In women, ther e was littl e d ifferen ce between the epide rmoid a nd ade no carcinoma grou ps a nd, ind eed , th e ade no carci noma five-year relat ive surviva l rat e (55 per cent ) exceede d that of the epide rmo id gro u p (48 per cent ): Hukill a nd St ern ha ve suggested that adc noca rcinom as of th e solid ana plast ic vari ety have a less f a vo r a bl e outloo k than the a denosq ua mo us or the highl y di fferentia ted ca rcinom as. Thus, th e literatu re difT.rs with respe ct to th e prognostic ignifi can ce of histo logic type, with greate r ran ge of va ria bility a tt rib u ted to th e ade noca rcinoma gro u p .
Surgical T reatm ent: The consideration for opera bility wou ld indi cat e the ab sence of med ica lly cont ra indicating factors, suc h as significan t card iac . hepa tic, r ena l and/ or pulmona ry disea ~ that would obviate a ny indi cated extirpativ pro cedure. Any urgical pr ocedure directed a t the pr imary tum or, whether for cure or for palliat ion , will be conside red as trea tment; however, th e proportion of the att empted excisiona l proced u res with inten t to cure w ill de termi ne the rat e of resectability. T he average ann ua l ra tes of t h o ra c ot omy and re cction in men a nd wom en d id not va ry significa ntly over tim ' or betw een th e sexes (T able 6 ) . App roximately 40 per cen t of patients who u nde rgo surgery each yea r have resectable disease. In a recen t report of the End Results Eva luatio n Program. the overa ll rate of resecta bility for men with lu ng ca ncer was 26 per cent as com pa red with the ra te of 23 per cent for women: In 51 per c mt of th e pat ients, surgical res zction was performed for non-localized
TA DLI' 6 AVERAGE A :-J :-I UA J. R ATI' S* 01' T IIORACOTO:lIY A:-:Il R 1:SEl:T10 :-: 1:-1 \\. II I'n : l\h::" AND W O:lm :-: WITII CARCt:-:O:lIA 0 1' L i :-:1: A:-:\ ) BRO:-: Cll tl S. M E:lIOJUAI. CI::-':T "R 19'19 - 1955 A:-':U 19 56- 1962 191 9- 1955 T h oracotomy R esec t ion
191 9- 1962
1956·1962
~ 1 " 11
\ VOIlIl'1l
1\1" n
\ \' 0 1111'11
33. 8 15 .5
3 1.8 15 .3
34. 1 12.0
22 .0 9 .7
* R a tes and stan d a rd d eviat ion s a re exp ressed a s percentages.
M en
:1-I .0 ± 3.2* 13.1l± 3.·1
\\' o lll e n
26 .9± 10 .7 12.5 ± 6 .5
1949- 1962 All Stages Relati ve Survival Ra tc S.E.*
T he factors of sex, stage of d isease, re ectability and histop athology represent m a jor prognostic va riables. A d d i t io na l factors, suc h as race, socio-economic sta tus, nature a nd duration of presenting sym ptoms, size a nd locati on of tumo r, presen ce of blood vessel invasion , extent of surgi ca l procedure and prim ary or adjunctive rad iati on th era py have received em phasis in the past. O ur d at a did not perm it ana ly is of corn; pa rati ve survival experience by race or social class; however, in the r ep ort of the Ca lifornia Tu m o r Registr y, the five-year relativ e surv ival rat e in men with localized disease tr e at ed at a priv at e hospita l was nearl y five tim es greater than that experj, enced by cou nty hospit al pati ents. It was not ed th at the operability rate in private pati ents with localized disease wa s twi ce th at of county hospit al pati en ts.' IIlu trating with Venn diagra ms of sym bolic logic, Feinstein" conce pt ua lized a classification of pulmon ic and extra-pulmonic sym ptoms that served to demonstrate the rat e of tumor gro wth a nd pati ent survival. H e recogniz ed th at the meaningful rc conj, ing of subjec tive manifestations of diseas e requi red a minimi zing of pati ent and physicia n e r ro rs of omission and com mission.
Localiz ed Relative Survival S.E.* Rate
0·6 months 0-1 ycar 0-3 ycars 0-5 years
63.9 48.4 3 1.1 17.2
2.8 2.8 2.8 3.3
60.8 53 .9 36.4 29.1
4.1 4.1 4.8 5.6
\Vomen 0·6 mon ths 0- 1 ycar 0-3 yea rs 0-5 year s
68.5 57.2 38.2 26.5
7.0 7.0 8.0 9.5
77.4 64 .4 52 .6 48 .8
7.1 7.1 8. 1 10.6
the Chest
D IS CUS SI ON
T ABL E 7 - RELATIVE S URVI VAL RAT E S· FO R S U RGI CALLY T RI: AT E D W IJIT E M E N A N D WO~I E N W ITH CA lt CINO~IA 01' L U N G A N D BRO :-lCH U S IIY STAGE 01' DI S EA S E , ~[ EMORIAL C E NT ER
Men
D iSC.1St s o (
W AT SO N AN D SCHOTTE N FELD
7°
*Survival rat es and sta nd ard errors of relative survival rat es a re expressed as percentages.
disease. T he survival rat es for the entire group of surgically treat ed patients did not differ significantly between the sexes (T able 7, Fig. 3 ) . Among the surgically treated localized CLL'ieS, and within the broad confidence limits occasioned by the li m i t e d numb er of cases, the survival rates were consistently higher in women. T hese observations para llel recent reports that em phasized the more favorab le survival in women with surgically tr eat ed cancers of the lung..·• 100
80 60
Cases 358
Mal~ A II Stages
154
- - Localized Fema--les: - All Stayes
53 27
- - - - Localized 10
o
2
3
Years alter Initial Treatme nt
5
3: Relative survival rat es for surgically treat ed whit e men and wom en with carcin oma of the lung and bronchus , by stag e of disease, Memor ial Ce nter , 19·19-196 2.
Fl la :nE
Volu me H , N o.1 J anuary. 1968
SU RVIVA L 1:-;' CA:-;'CE R OF BRO N CHUS AND LU NG
Nevertheless, th ese subsets of sym ptoms associated with lun g ca nce r reprc cnted impor tant variables for estimating prognosis and evaluating tr eatment. In a series of 271 men with localized lun g cancer detected by routine c hes t xrays, Steele" describ ed th e linear relati onship of tumor size to survi val. In th e recent report of Co nnelly et at,$ th e five-year relative surviva l rates in s u rg ica lly tr eat ed patients wit h locali zed lun g ca nce r were high est for both sexes for tumors origina ting in th e middle lobe, a nd least for men wh en o r ig i na t i ng in th e lower lob es and for wom en, in the main bronchi . Our data did not permit meaningful description of the relati onship of tum or size and location to su rviva l. Co llier et at: reported 83 per cent five-year su rviva l in surgica lly treat ed lun g ca ncer patients without demonstrable blood vessel and lymph node invasion. Id entification of circu lating ca nce r cells in peripheral vein s or in effl ue nt veins from th e tum or bed will require further study as to th eir progn ostic significa nce .' The valid assessment of various programs of primary a nd ad junctive th erapy requires rand omi zed alloca tion of compa rable subg ro u p s of pati ents. Shimkin et al" conclu de d that su rvival a fte r excisiona l surgery was pr imarily determined bv extent of disease and not by th e application of more radi cal extirpati ve measures. Our analysis did not suggest an y trend of increasing awareness or ea rlier detection of lung cance r, nor did it indi cat e an y imp rov em ent in overall survival. Gilbertsen" reviewed th e e x pe r ie nce of th e Can cer Detection Ce nter at th e U niversity of Minnesot a a nd concluded th at an adequ at e screen ing meth od for ea rlier dete ction of asy m ptomatic lun g ca nce r was not availa ble. While routine periodi c x-ra y examin ati on of the chest in asymptomatic person s 45 yea rs of age and older has not been productiv e in terms of frequ ency of det ection of I u n g ca nce r, nor in term s of enhancem ent of s u rv iva l in th ose cases so d et ected ," Bou cot et al' have em phasized t he need fo r ca reful, sem i-annual roent-
71
gcnographic creening of high- risk indi vidua ls-s-t hose who have smoked heavily for a long time and those who have symptoms, such ,L<; coughing. The overwhelming thrust against lung cancer morbidity and mort ality will ema nate undoubtedly from primary preventive measures such as complete cessation of tobacco inha lation, and not from future refinements of diagn o tic and th erapeu tic techni cs. S Ul\I l\I ARY
The su r V iv al experience has been reviewed for 3, 124 lung cancer patients diagnosed at the Memorial and J ames Ewing Hospitals during the period 1949-1962. At least 40 per cent of case s demonstrated distant disease at the time of initial diagnosis and there was no indi cation during the later years of an increasing proportion with localized disease. While there was no significant improvement in the overall relativc survival rat es during this period, th ere wa a two- to three-fold in crease in th e thre e- and five-year survival rat es for both men and wom en with localized disease. Adenocarcinoma and terminal bronchi olar ca rcinoma were twice as common in the women, while epidermoid and oat cell carcinoma predomin ated in the men. Localized termin al bronchiolar carcinoma exhibited ign ificant survival advantage for both men and women. Surv ival experience was least favorable for those patients with oat cell carcinoma and did not differ significantly for adenocarcinoma and epidermoid c; rc in o m a . Among the surgically treat ed localized cases, the sur vival rat es were consistently higher in women . Other future effects of primary and secondary preventive measur es in lung cancer were assessed. R ESU M EN
La su pervi ven cia de 3, 124 pa cien tes d e ca ncer pu lmonar d iagnostica dos en los h osp ital es M emoria l y j am es Ew ing d ur a nt e el p eriodo 194962 , es objeto de rev ision. POl' 10 mcnos cl 10% de los cases prcscn tah an parr ici pa cio n a di sta ncia al iicmpo d el di agnostiro in ir ial y no se observe en aiios succsivos a u uu -mo a lguno en la p roporc ion d e case s ron le si611 localizad a. Si bien 110 11\Iho mejeria d e sign ifica cidn en la su pc rvive nc in de co nj unio en est
WATSON AND SCHOTTE>: FELD
72
period o, si se rcgistr6 una proporcion dohl e 0 tripl e d c superv ivc nc ia quinq ucnal en los casos con lesion loca lizad a , ta nto en h ombrcs co m o en muj crcs, En t re las m u jcres c l ad cn ocarcino m a Y 1'1 ca rci no m a bronq u iolar terrnina l fu eron d os vcces ma s fr 'C UI' IItCS, a l pa so q uc en t re los hombres prcd ominaron cl carcinoma cp id c rJno ide Y 1'1 tipo oa t cell. EI ca rcino ma br onquiolar terminal localizad o, pr escnt o mejor es probabilidadcs d e su pe rv ivcn cia par a a mbo s sexos. E1 ca rci no ma ii po oat ce ll fue c l d e p ro nostIco monos Iuvor ab le. No h ubo d ifcrcnc ia n ot abl e en cuanto a SII superv ivencia en tre el ad cno carcinoma y 1'1 ca rcinoma c pi de r m o ide . Ent rc los cases loca lizados t ratados q u iru rgica men te la superv ivcncia fue cons istent e ment e m a yor ent re las m ujer es, Se cva lua n otras vari abl es d el p ron6sti co y la cfcc iividad p resen tc y fut u ra d e la s mcdidas prcvcnt ivas de ord cn prima rio y se cun d a ri o.
2 3
4
5
6 7 8
R EFERE:-:CES BOUCOT, K . R ., COOPER, D. A., W EISS, W . A:-> D C ARNAHAN, W. J.: " C iga re ttes, cou gh and can cer of th e lung " J A M A , 196: 985 , 1966 . Ca ncer Registrat ion an d Surviva l in California . Calif ornia Tumor R egistry, State of Ca lifornia Dept. of Pub. H ea lth , 1963, pp . 176 - 189 . CHRISTOPHERS ON, W. M. : " A re-evaluation of the significance of circulating cance r cells in the periphera l blood," from the text R ecent A d va1lces in th e Diagn osis of Canc er, Y ear Book Medi ca l Publisher s, Chica go, 1966 . COLLIER, F. C ., BLAK EM ORE, W . S ., K YLE, R . H ., E NTERLINE, H . T ., KIRDY, C . K . AND J OII:-> SON, J. : " Carci no ma of th e lun g: Iacturs whi ch influen ce five-year su rv iva l with special refere nce 10 blood vesse l in vasi on ," Ann . Surg., 146: 41 7, 195 7. CONNELLY, R . R ., C UTLER, S. J . AND BAYLIS, P.: " End results in cance r of th e lun g : comparison of ma le and female patients," J. Nat . Can cer I nst., 36:2 77 , 1966. C UTLE R, S. J. AND EDERER, F .: " M ax im um ut ilizati on of th e life table method in an al yzing survival," J . Chr onic ou., 8: 699, 1958 . . . EDER ER, F. : " A sim ple method for det ermllllng sta nda rd erro rs of surviva l rates, with tab les," ]. Chron, D is., 11: 632, 1960 . EDER ER, F., AXTELL, L. M . AND C UT LER, S. J.: "T he relative sur vival ra te : a sta tistica l methodo logy," Na t. Cancer l nst, Mon ogr ., 6: 101, 1961.
9 EIlERI;R, F . ANI> M ERSHEIMER, W . L.: " s d ifferences in th e su rv iva l of lu ng cance r p e " tien ts," Can cer, 15 : 42 5 , 1962. a10 EISE:->II ERG, H ., SIIA~IE S , J . ~l. , H OLLO'" • W. r.. ANI> BARRETT, H . S. : " C a nce r o f bron chus an d lu ng : Conn ecti cut, 19 35-195 9 ~ J. Ch ron , Dis., 17 : 10 33, 196'k ' . 11 FEINSTEIN, A. R . : " Symptomatic patt er ns b'I o ologic behavior, a nd progn osis in cancer o f' t.h lun g. Practica l appl ication of Boolean al ge b e a nd clin ica l ta xon omy," A nn . Int ern . M 2 1:27, 1961. " 12 G ILllERTSEN, V . A. : "X-ray examination t~lc chcst. An unsa tisfact o ry method of d er o f n on of ea rly lu n g ca nc er in asymptomatic ind~ vid ua ls,' J AMA , 188: 1082, 19 64 . 113 qll.IJ F. RTSI;:-:, V . A . : " The poten ti a lity for su viva l enha nce me n t by exped itious d et ec tio n r neop lastic di seas es," ( Ed . Ariel 1. 1\,[. ) Pro o f gress in Cl ini cal C anc er, G run~ and S;ratto eNew York , 1966 . n, 14 Hlm~I A N . D . L . AND C RITTENDEN M . : "D l' S triburi on uf pri mary lung carcino~na in rel tion to ti mc a s d et ermi ned by h istocheml j-,a -I . .. J• N at . Can cer I nst ., 27 : 12 27, 19 6- a. tee I1I11CS, I 15 I! UKILL, P. B. AND STERN, H.: " Adenoc a r' ~lIlom a of t!IC lu ng : h isto log ical fa ct ors affe c t.: mg pr ognosis. A stu d y of 38 patients with r secti on and 5-y ea r follow -up Canc er 15· 5 0~ 196 2. " . "T , 16 K RI;YIIERG, L . : " H isto logical lu ng ca nc er tYP e A mor ph ological an d b iological co rre l a tion~ ; A ct a Path . M icrobi al, S can d, ( Su p p!. ) 15 , ' 7, 1962. ' : 17 M E R s II EI ~m R , W. L . ANI> EDERER, F . : " E.nd resu lts eval ua tion of ca ncer of th e lung a n d b.run c h u~," in P roceedings of th e Fou rth JV a _ t io n al Can c e T Con feren ce, J. B. Lippincot.t. Ph iladel ph ia . 1960. • 18 SIII ;\IKIS, 1\1. B., CONNELLY, R . R ., MARCtJ S S. C . ANll C UTLER, S. J.: " Pneu m on ecto n l ' an d lol~ectomy in br on ch ogen ic ca rcin oma . co m par rson of end results of the O verholt a n d O chsner cl inic s," J . T ho r. Cardiouas. Surg H :503, 1962. " 19 STEELE, J. D . : "Carcinoma of th e lun g" ( t h e UC LA Int crd epartmcma l Conferen ce ), An n I ntern, M ed ., 6 '~ : 180 , 1966 . . 20 WATSON, W . L . : " Five-yea r su rvivors in lung ca nce r. A s t u d y of 3,0 73 cases," Am er. J R oent ge n. , 79 : 488, 1958 . . 2 1 WATSON, W. L. AND BERG, J . W.: " O a t Ce ll lu ng ca ncer," C II1lCer, 15 : 759 , 1962 . 2:! \ V t\ " S O N , W . L . ANlJ S~II TII , R . R . : " T crrn in n ] bro nchio la r or 'a lveola r ce ll' ca nce r of lu n g . rcport of 33 cases,' J A M A , 147 : 7, 1951. '
ti; .
eJa
tI
..t
For rep rints, please write: Dr. Watson , 3·10 Ea s t 77 th St ree t, New York 10021.
EVAL UAT ION OF FR EEZE DRIED KV El}, [ RE AG ENT sta ble. the advanta ges In clinica l pract ice ot an ettec_ t ive Irtx-ze-dr icd propa ratlon do not requ ire em pha_ sis . Th · posit ivity ra te In the pr esent st udy IncH_ ca tes Iha l rreeze-dr teu K ve lrn reagent is a po t ~n t test ma ter ia l in the diag nosis 0 1 sarcoidos is.
In active sarcoidosis freeze-dried Kvelm-t est mater lal gives derm al rea~ti ons of Identi ca[ macroscopic aPl'ea ranee to those produced by flu id reagen t. No " Ialse positive " reactions have so fa r been record ed with Irecze-drlcd antigen. Fre eze-dr ied antigen appear s to reta in its potency for long periods at room temperature .
While lIuid K vclrn -t es t substance Is remarkabl y
K'·NNWY. \VI . 1'. U . : " An eva lu at ion o f Freeze-d ried Kvc i rn rcagcm; " Brit. t. Dis. CluSl .• 6t: ·\0. 1967.
L.
' VATS ON , · · "1.1l. ANIl
Dxvrn
S CII OTl"E:\FELO, " I.O : 'Hf
N ew Y ork, N ew Y ork
O
in untreated patients. from th e date th ey were first seen a t Memorial Center. The point s in time for computing rates of survival were set at mon thly intervals for th e initial six months and at three-mon thly intcrvals for th e subseq uent 54 months. When th e d ata permitted , the experiences of two coho rts of pati ents. 194 9-1 955 a nd 195()19() 2, were com pa red, A d j us t III c n twas made for sex and age differen ces in norm al mortality expecta tion by com puting relative su rvival rat es. T he relat ive sur viva l rat e is th e ra tio of the oh ervcd sur vival rate to th e su rviva l rat e expected in persons drawn from th e gene ral popul ati on at a com pa rahlc point in tim e with th e same cha rac teristics 1)\' race, sex and age as the pati ent group. 'T his adj ustme nt permit meaningful com pa rison of men and w om en patients a nd of patient grou ps tha t ma y d iffer with respect to age.' The standa rd error of the relati ve . u rv iva l rate was comput cd to esta blish confide nce limits and to pe rm it assessme nt of statistical significa nce of observed di fference .'
I NT RODU CT IO N
4000 I'AT IE l': T S WITI[ L U N G CANce r ha ve been see n a t th e M em ori al Ce nter for Ca nce r a nd Alli ed Diseases since 1930. Since 194 9. privat e a nd ward lu ng ca nc T cases ad m itted to th e M em ori al a nd J am es Ewin g Hospital s have been ente red int o th e Ca ncer R egistry a nd th e reco rds pro cessed by m ean s of pun ch ca rds a nd an electron ic co m pute r. I n addition , t he thora cic s '1"\' i c c has abstract ed clin ica l a nd pathologi c inf ormati on on all lung ca ncer cases treat ed sinc e 19 30 . The data deriv ed from th ese sou rces provid e th e m at erial for thi s r view of su rv ival a mo ng tre ated, as well as untrea ted ca ncer cases di agn osed during th e peri od 1949 to 1962 . VE R
M ETH OD O F A NALY SIS
The su rvival ra t wer e com pu ted b y th e life-table me tho d, whi ch permitted maxim um ut iliza tion o f a 11 ava ilable su rvival in forma tion lip to th e m ost I' 'cen t d at e of follow-u p in J a nua ry, 19() ().· Follow-up informati on was com plete for more th an 99 P ' I' ce nt of th e pati en ts. Su rviva l tim e was m easured from the d ate of tr eatment , or
R ES ULT S
.·lgc : The age distribution bv race a nd sex for pa tient s with ca rcinoma of th e lung a nd bronch us is s ho w n in T able I. T he fre-
* C h icf of Thoracic Servi ce . Em eri tus , M em orial C e nter for Cancer a nd Alli ed Dis eases. * * Di rect o r of Clinica l St a tisti cs, and Assistant D ir~ c to~. Admitt ing and Diagnostic Clinic. M emorial C. 'liter for C ance r an d All ied Di sea ses. TAIlI. E I -
A C E DI S TRllI lJ Tl O N II\" RA e \·: A :>;J) S EX POR P ATI E :>; T S W IT II C ARCI :>;O)\ ,\ O J' 1. 1' :>; ' : A N Il BRO :-:C:J1 U S , r- I DI OR IAI . CE:>;TE R ,
19·1 9- 1955. 1 9 5 6-1 91i ~
Non-whi te
Whit c 1949·1955
M en T o ta l Und er 45 45 -51 55-64 65 - 7·1
0"" "
75 a lii! M ed ian a ge
1328 81 340 526 3:15
(6) * ( 26 ) ('10 ) ( 25)
-I( ; (:ll
:\ v--ru ~'-' a~('
*(
Womcn
) Pe n "' utage age
59. 1 51l.:>
239 28 (1 2 ) 6'1 ( 27 ) 81 (3 4) 51 ( 2 1) 15 ( 6) 57 .9 5 7.5
Womcn
Men 130 7 78 ( 6) 288 (22) 55 1 (.l:!) 3:12 ( 25) 5/1 (-I ) 59.7 ':)9.1
250 33 78 69 56
( 13) ( 3 1) ( 28 ) (22 ) J.I ( 6) 56 .5 56.a
d istri hur io u lIlar not total 100 b vca usc
65
1956 -1962
19·19-1955
1956-1962
Mcn 42 3 ( 7) 16 ( 38) 14 ( 33) 7 ( 17) 2 (5) 55.9 56.5
or round ing.
Womcn 7 2 3
2
Men 43 2 16 17 8
( 5) (3 7) ( 39) ( 19 )
- (0 ) 56.6 56.:1
wome n 10 1 5 2
66
D isc .1SC S o f
WAT SON AN D S C H OTTE NFE LD 100 &l
MALES:
60
-
- - 1949- 1955
.'"
~
able at first h os p it al discharge, including that obta ined from exam ination of surgical specimens. L ocalize d ca ncer is con fine d to th e site of origin with out specifica tion as to the size a nd includes direct exte nsion with_ out metastases. R egion al c a n ce r includes clinical and / or microscopi c evidence of direct extension of d is e as e to neighboring organs, tissues or to region al lymph nod es. D istant ca ncer includes clinical and/or microscopic evidence of sprea d of disease to organ s or tissues beyon d th ose immedi ately d rain ing or bordering th e site of origin. The distribution of m en and women a t th e tim e of initial eva luation for th era p y as shown in T ab le 2 was not significantly different. At least 40 per cent of the cases demon strat ed d istant disease a nd th ere Was no indicati on of a ny relati ve increase ove r tim e in th e percen tage with locali zed ca n cer. The six-month, one-yea r, three-year a n d five-year relative survival rat es by stage o f disease for men and wom en without regard to treatm ent a re summa rized in Table 3 a nd Fig. I a nd 2. There was no significa n t improvem ent in t h e overa ll relative SUr_ vival rates for the men a nd wom en , a n d no essential d ifference between th e sexes . Am ong th e treated and u ntrea ted ea es with
Cases 1328
1956 - 1962 1301
FEM~I£~ 1949 - 1955
239
- - - - - 1956 - 1962
250
'"
~20
.
:::>
Vl
.~
0; 0:
10 8
I
o
2
I
I
3
4
Years aller Initial Treatment
I : Relative survi va l rates for white men and women with carcinoma of th c lun g and br onchus, all stages, 1949-1955 and 1956-1962, M em orial Cen ter. FIG U RE
qu ency distributions approximated normal curves and exhibited stability over time. Among the w hi te patients, the majority were with in the age int erval, 55 to 64 . S tage of Disease : The classification of pati ents by stage of disease was based on all information avail100
th e Ch e,t
Ma~ 1949- 1962
Fe~~:.s~ 1949- 1962
Cases 481
79
60
10
o
2
I
3
Years afte r Initial Treatment
I
4
5
F IG U RE 2 : Rela tive sur vival rat es for whi te men and women with ca rc inoma of the lun g and bronch us. localized d isease, 1949- 1962, Memoria l Center.
Volume H . 1"0. 1 ) , n u,ry, 1969
SU RVIVA L I • CANC E R O F BRON C HU S AND LUNG
'rAllLI, 2- D ISTRlIlUTI0:-; OF PATm :-;TS, \ \' Ill n : }.IE:-; A:-; 1l W O ~lE: :-; , WITII C A R C I:-;O ~ I A 01' L u x e A:-:1l BRO:-: ClI l' S Ae COIWI:-;C TO STAGE OF D ISI':ASE AT TDlI' 0 1' I:-: ITI.\ I. E \·AI.t ·ATIO:-; FOR TIII-:RAI'Y, ~ I E ~I O RI AI. C E:-;T ER . 19·19.1 955 A:-;1l 1956 · 1962 Stage of D iseas:A ll st ages Loca lized R egio n a l D i ~ l a nt
Unkn own
19 19-1955 Wom en M en Per Ce n t Number Per C ent N um ber 13 28 242 25 9 55 ,1 2 73
100.0 18 .2 19 .5 '11.7 20 .6
2:1:1 39 49 93 52
local ized disea se, th ere was a tw o- to th reefold increase in th e three- and five-yea r relative survival ra tes for both men a nd wom en . :\ mong th e m en with localized disease, th e six-mo nth and one-y ea r surv iva l rates were somewha t better th an a mo ng th e wom en , bu t th is ad va ntage was not .ubscq ucntly m a nifested .
II islology 0/ T um or : The d istri butions with in th e sex gro ups h y histologic type were st riking ly different (T a ble 1 ) , The histop athologic diagn oses were int erpret ed from biopsicd or surgically resected tissues in 90 per cent of instances a nd in th e r em ainin g 10 per cent from sp ut um , bron chi al washings or pleu ral fluid. .'\ m o ng th e design at ed cell types, ade noca rcinom a a nd termi nal bron chiolar ca rcinoma
100 .0 16.7 2 1.0 :19 .9 n :1
1956- 196 2 \Vom en M cn Number Per Ce n t Per Ce nt N um ber 130 7 239 25 3 60 3 2 12
250 40 57 110 ·13
100.0 18.3 19,4 46 . 1 16.2
100 .0 16.0 22.8
H .O 17.2
or hron chioloalveolar ca rcinoma (grou p 2 of Krcyhcrg ) formed a larger proporti on ( 25 per cent ) and were twice as common in th e wom en , while epidermoid a nd oat cell carcinoma (group I of K rcyberg ) predominated (53 per cent ) in the men . :\ d isturbingly large prop ort ion of tumors were un classified and anaplastic in both sex grou ps and th e minor shift in hi tology exhibited by th e 1956-196 2 cohor t of wom en reflected relative increases in adenocarcinoma and term inal bronchiolar ca rcinoma or bron chioloalvcolar carcinoma. H erm an and Crittenden" noted in th eir postmort em material th at ab out 30 per cent of tumor. were poorly differentiated carcinomas, "ith th e technique of differenti al sta ining for keratin and m u c in and th e classifica tion of cell type a d voc a t e d by
TAllL E 3- R I,I.ATI\·E S UR\,I\·AI. R ATES* FOR W IIITE 1'.11-::-; A:-; II \\' 0 ' 11-::-; WITII CAR CI :-;O~IA OF L u x e A:-:U BRONCII US IIY STAca : OF D ISI':ASE, 1 1r" I OJUAI. C E='TER, 19·19- 196 2 Local ized All Sta ges
Relat ive
R elative
Survi val
M en 0 -6 m onth s 0 - 1 year 0 -3 years 0 -5 years \Vo m en 0 -6 m ont hs 0 - 1 year 0- 3 yea rs 0 -5 years
Ratc
S.E.*
19'19-55 1956 .6 2 1949·55 1956-6 2 1949 ·55 1956-62 1949 ·5 5 1956 -6 2
32 .3 40 .8 18.4 22 . 1 6 .7 6 .2 5. 6 3.9
1.5 1.5 1.5 1.5 1.I 1.0 1.I 1.0
1949 -5 5 1956-6 2 1949-55 195 6-6 2 19'19-55 1956 -6 2 19 19 -55 1956 -6 2
35 .4 41.0 1U.7 20 . 1 6 .7 6 .9 '1..1
3.5 3.5 3.0 3.0 2.1 2 .0
.1.5
Su rvi val Rate
-
') _ .1
2.5
S .E .*
19,19-62
58.3
2.5
19·19-62
'12. 7
:!oS
1949-6 2
21.6
2.5
1949·62
17.0
3.0
1949-62
4 7.0
6. 0
1949 -62
3 1.0
6. 0
19-19·62
20 .:1
6 .0
19·19-62
17.9
a.n
* S u r \'i \'al rat es and stan d ard (' ITOrs o f rclar ivr- su rv iva l rat es a re expressed as pcrcc rua gcs.
WATSO N A ND S CHOTT ENF E L D
68
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E o
~ ?;
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s
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~
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cu
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1: 71: ,, - - I
- - -.,c E o
?;
~..,
or
I
N
------ -
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cu
~
ex>
D iseases oi th e Chest
Kreybe rg," th ey reviewed th e u nd ifferen tiated sub-gro u p a n d observed subs ta n tial inc rease in th e adenoc arcino mas . For localized disease, the relative su rviva l rates in termin al bronc hiolar ( bronch ioloalveola r) carcinom a indi cat ed significa nt advant age for both men an d wom en with a grea ter sa lvage am ong th e latter (T able 5) . Previou s rep orts from Mem orial Ce nter hav e noted th at pat ien ts with termin al bron chiolar (bronchioloalveola r ) ca rcino ma had th e high est rat e of resecta bility a nd th e most favorabl e progn osis, while those with oat cell ca rcinom a dem onstrat ed the lowest favora ble rat e of rcscctabilirv and the least . .rva I .20 ·22 I n t he. pr esen t review, a pproxsu rv chi ola r bron l ina term of ima tely 2 1 per cent zed III locali as ed cell ca ncers were classifi were cent per 75 both sexes, a nd of th ese, th at d observe resected. H ukill an d Stern" p grou a as the bron chioloal veolar ca ncers difnot exhibited a varying course and did fer in prognosis from the ade noca rcinom as, a pa rt from those bron ch ioloalv colar tumors of unicen tr ic circum scribed origin th at w er e readil y resecte d. " The relati ve surviva l ra tes at three a nd five years of pat ients of h oth sexes with epide rm oid tumors were not significan tly differe nt. Although the pro portion of epidermoid tum ors classified as localized was com pa rable to tha t of the termin al b ron chiola r cell, the rat e of resecta bility for this group was 45 per cent in me n a nd 57 per cent in w om e n . In th e ade noc a rcino ma sub-grou p, th e limited numbe r of cases with localized disease did not permit meanin gful statistical com parison betw een men a nd wom en. In this review a nd within th e broad confide nce limit s of our data , th e relative surviva l rat es at th ree and five years for men with ad enocar cinoma , althoug h some wh at superio r, did not differ significantly from th e gro up wit h epide rmo id can cer. Among the men with ade nocarcinoma, th e proporti on with localized disease was 11 per cent, and of th ese, 40 per cent were resected . The Ca liforn ia Tumor Reg istry report ed that m en with localized adenoc arcinoma of the lung exhibited a less rapi d
Volume H . No .1 January. 1968
69
S U RV IVA l. I >: C ANC E R O F llRO " CIIU S A"D LUNG
TABLE 5- RELATIV E S URVIVAl. R ATES* I'OR \ \' 1I1T1: ~ I L. · A :" I> \ \' O:llf.. · WITII LOl:AI.IZEI, CARCI:-IO:lIA OF L U:-IC A:-ID BRO:"CII ' S llY I IISTOI.OI;(C T YI'E. ~h: :lI OR IA I. C E:"TER. 1 9 · 1 9 · 1 9 6 ~ R ela tive Surviva l R a te - - Loca lized D isease 11-:1 Years S.E. * l J.:j Yea rs S . I~ . * S .E . * 0· 1 Year H istologic Type All h istologic types M en W omen Epid ermoid ( sq u amous) M en W omen Terminal b ronc h iola r M en W o men Adenocarcinoma M en W om en
42.7 3 1.0
2.5 6 .0
2 1.6 20 .3
2.5 6.0
17.0 17.9
3.0 8.0
41.8 56 .3
3.6 7.3
22 .0 1-1 .1
3.6 6.0
13.9 1·1. 1
3.8 6. 0
68 .0 60 .1
7. 1 7.0
38 .-1 50. 1
7. 1 7.5
32. 9 45 . 1
8 .7 8.5
61. 2 **
7.2
:10.6
7.2
30 .6 **
8 .2
**
*Survival rates a nd sta ndard e rr ors a re ex p ressed as percenta ges. ** L ess th a n 10 ca ses.
rate o f cu m ulative mortality th a n those with e pid erm oid ca ncer: The d ata of th e Co nnecticu t Tumor Registry d id not ind ica te a nv consiste nt d ifference in th e su rv iva l rates for men and w om en by histologic types, alt ho ug h th e sq uam ous cell type offered a slightly poorer progn osis." These findings di ffered f r o m th ose of Co nnelly el al/ where th e five-yea r relative su rviva l rate fo r localized tumors in men was 41 per cen t for th e sq ua mo us cell type and 16 per cen t for th e a de noca rc i no ma gr ou p. In women, ther e was littl e d ifferen ce between the epide rmoid a nd ade no carcinoma grou ps a nd, ind eed , th e ade no carci noma five-year relat ive surviva l rat e (55 per cent ) exceede d that of the epide rmo id gro u p (48 per cent ): Hukill a nd St ern ha ve suggested that adc noca rcinom as of th e solid ana plast ic vari ety have a less f a vo r a bl e outloo k than the a denosq ua mo us or the highl y di fferentia ted ca rcinom as. Thus, th e literatu re difT.rs with respe ct to th e prognostic ignifi can ce of histo logic type, with greate r ran ge of va ria bility a tt rib u ted to th e ade noca rcinoma gro u p .
Surgical T reatm ent: The consideration for opera bility wou ld indi cat e the ab sence of med ica lly cont ra indicating factors, suc h as significan t card iac . hepa tic, r ena l and/ or pulmona ry disea ~ that would obviate a ny indi cated extirpativ pro cedure. Any urgical pr ocedure directed a t the pr imary tum or, whether for cure or for palliat ion , will be conside red as trea tment; however, th e proportion of the att empted excisiona l proced u res with inten t to cure w ill de termi ne the rat e of resectability. T he average ann ua l ra tes of t h o ra c ot omy and re cction in men a nd wom en d id not va ry significa ntly over tim ' or betw een th e sexes (T able 6 ) . App roximately 40 per cen t of patients who u nde rgo surgery each yea r have resectable disease. In a recen t report of the End Results Eva luatio n Program. the overa ll rate of resecta bility for men with lu ng ca ncer was 26 per cent as com pa red with the ra te of 23 per cent for women: In 51 per c mt of th e pat ients, surgical res zction was performed for non-localized
TA DLI' 6 AVERAGE A :-J :-I UA J. R ATI' S* 01' T IIORACOTO:lIY A:-:Il R 1:SEl:T10 :-: 1:-1 \\. II I'n : l\h::" AND W O:lm :-: WITII CARCt:-:O:lIA 0 1' L i :-:1: A:-:\ ) BRO:-: Cll tl S. M E:lIOJUAI. CI::-':T "R 19'19 - 1955 A:-':U 19 56- 1962 191 9- 1955 T h oracotomy R esec t ion
191 9- 1962
1956·1962
~ 1 " 11
\ VOIlIl'1l
1\1" n
\ \' 0 1111'11
33. 8 15 .5
3 1.8 15 .3
34. 1 12.0
22 .0 9 .7
* R a tes and stan d a rd d eviat ion s a re exp ressed a s percentages.
M en
:1-I .0 ± 3.2* 13.1l± 3.·1
\\' o lll e n
26 .9± 10 .7 12.5 ± 6 .5
1949- 1962 All Stages Relati ve Survival Ra tc S.E.*
T he factors of sex, stage of d isease, re ectability and histop athology represent m a jor prognostic va riables. A d d i t io na l factors, suc h as race, socio-economic sta tus, nature a nd duration of presenting sym ptoms, size a nd locati on of tumo r, presen ce of blood vessel invasion , extent of surgi ca l procedure and prim ary or adjunctive rad iati on th era py have received em phasis in the past. O ur d at a did not perm it ana ly is of corn; pa rati ve survival experience by race or social class; however, in the r ep ort of the Ca lifornia Tu m o r Registr y, the five-year relativ e surv ival rat e in men with localized disease tr e at ed at a priv at e hospita l was nearl y five tim es greater than that experj, enced by cou nty hospit al pati ents. It was not ed th at the operability rate in private pati ents with localized disease wa s twi ce th at of county hospit al pati en ts.' IIlu trating with Venn diagra ms of sym bolic logic, Feinstein" conce pt ua lized a classification of pulmon ic and extra-pulmonic sym ptoms that served to demonstrate the rat e of tumor gro wth a nd pati ent survival. H e recogniz ed th at the meaningful rc conj, ing of subjec tive manifestations of diseas e requi red a minimi zing of pati ent and physicia n e r ro rs of omission and com mission.
Localiz ed Relative Survival S.E.* Rate
0·6 months 0-1 ycar 0-3 ycars 0-5 years
63.9 48.4 3 1.1 17.2
2.8 2.8 2.8 3.3
60.8 53 .9 36.4 29.1
4.1 4.1 4.8 5.6
\Vomen 0·6 mon ths 0- 1 ycar 0-3 yea rs 0-5 year s
68.5 57.2 38.2 26.5
7.0 7.0 8.0 9.5
77.4 64 .4 52 .6 48 .8
7.1 7.1 8. 1 10.6
the Chest
D IS CUS SI ON
T ABL E 7 - RELATIVE S URVI VAL RAT E S· FO R S U RGI CALLY T RI: AT E D W IJIT E M E N A N D WO~I E N W ITH CA lt CINO~IA 01' L U N G A N D BRO :-lCH U S IIY STAGE 01' DI S EA S E , ~[ EMORIAL C E NT ER
Men
D iSC.1St s o (
W AT SO N AN D SCHOTTE N FELD
7°
*Survival rat es and sta nd ard errors of relative survival rat es a re expressed as percentages.
disease. T he survival rat es for the entire group of surgically treat ed patients did not differ significantly between the sexes (T able 7, Fig. 3 ) . Among the surgically treated localized CLL'ieS, and within the broad confidence limits occasioned by the li m i t e d numb er of cases, the survival rates were consistently higher in women. T hese observations para llel recent reports that em phasized the more favorab le survival in women with surgically tr eat ed cancers of the lung..·• 100
80 60
Cases 358
Mal~ A II Stages
154
- - Localized Fema--les: - All Stayes
53 27
- - - - Localized 10
o
2
3
Years alter Initial Treatme nt
5
3: Relative survival rat es for surgically treat ed whit e men and wom en with carcin oma of the lung and bronchus , by stag e of disease, Memor ial Ce nter , 19·19-196 2.
Fl la :nE
Volu me H , N o.1 J anuary. 1968
SU RVIVA L 1:-;' CA:-;'CE R OF BRO N CHUS AND LU NG
Nevertheless, th ese subsets of sym ptoms associated with lun g ca nce r reprc cnted impor tant variables for estimating prognosis and evaluating tr eatment. In a series of 271 men with localized lun g cancer detected by routine c hes t xrays, Steele" describ ed th e linear relati onship of tumor size to survi val. In th e recent report of Co nnelly et at,$ th e five-year relative surviva l rates in s u rg ica lly tr eat ed patients wit h locali zed lun g ca nce r were high est for both sexes for tumors origina ting in th e middle lobe, a nd least for men wh en o r ig i na t i ng in th e lower lob es and for wom en, in the main bronchi . Our data did not permit meaningful description of the relati onship of tum or size and location to su rviva l. Co llier et at: reported 83 per cent five-year su rviva l in surgica lly treat ed lun g ca ncer patients without demonstrable blood vessel and lymph node invasion. Id entification of circu lating ca nce r cells in peripheral vein s or in effl ue nt veins from th e tum or bed will require further study as to th eir progn ostic significa nce .' The valid assessment of various programs of primary a nd ad junctive th erapy requires rand omi zed alloca tion of compa rable subg ro u p s of pati ents. Shimkin et al" conclu de d that su rvival a fte r excisiona l surgery was pr imarily determined bv extent of disease and not by th e application of more radi cal extirpati ve measures. Our analysis did not suggest an y trend of increasing awareness or ea rlier detection of lung cance r, nor did it indi cat e an y imp rov em ent in overall survival. Gilbertsen" reviewed th e e x pe r ie nce of th e Can cer Detection Ce nter at th e U niversity of Minnesot a a nd concluded th at an adequ at e screen ing meth od for ea rlier dete ction of asy m ptomatic lun g ca nce r was not availa ble. While routine periodi c x-ra y examin ati on of the chest in asymptomatic person s 45 yea rs of age and older has not been productiv e in terms of frequ ency of det ection of I u n g ca nce r, nor in term s of enhancem ent of s u rv iva l in th ose cases so d et ected ," Bou cot et al' have em phasized t he need fo r ca reful, sem i-annual roent-
71
gcnographic creening of high- risk indi vidua ls-s-t hose who have smoked heavily for a long time and those who have symptoms, such ,L<; coughing. The overwhelming thrust against lung cancer morbidity and mort ality will ema nate undoubtedly from primary preventive measures such as complete cessation of tobacco inha lation, and not from future refinements of diagn o tic and th erapeu tic techni cs. S Ul\I l\I ARY
The su r V iv al experience has been reviewed for 3, 124 lung cancer patients diagnosed at the Memorial and J ames Ewing Hospitals during the period 1949-1962. At least 40 per cent of case s demonstrated distant disease at the time of initial diagnosis and there was no indi cation during the later years of an increasing proportion with localized disease. While there was no significant improvement in the overall relativc survival rat es during this period, th ere wa a two- to three-fold in crease in th e thre e- and five-year survival rat es for both men and wom en with localized disease. Adenocarcinoma and terminal bronchi olar ca rcinoma were twice as common in the women, while epidermoid and oat cell carcinoma predomin ated in the men. Localized termin al bronchiolar carcinoma exhibited ign ificant survival advantage for both men and women. Surv ival experience was least favorable for those patients with oat cell carcinoma and did not differ significantly for adenocarcinoma and epidermoid c; rc in o m a . Among the surgically treat ed localized cases, the sur vival rat es were consistently higher in women . Other future effects of primary and secondary preventive measur es in lung cancer were assessed. R ESU M EN
La su pervi ven cia de 3, 124 pa cien tes d e ca ncer pu lmonar d iagnostica dos en los h osp ital es M emoria l y j am es Ew ing d ur a nt e el p eriodo 194962 , es objeto de rev ision. POl' 10 mcnos cl 10% de los cases prcscn tah an parr ici pa cio n a di sta ncia al iicmpo d el di agnostiro in ir ial y no se observe en aiios succsivos a u uu -mo a lguno en la p roporc ion d e case s ron le si611 localizad a. Si bien 110 11\Iho mejeria d e sign ifica cidn en la su pc rvive nc in de co nj unio en est
WATSON AND SCHOTTE>: FELD
72
period o, si se rcgistr6 una proporcion dohl e 0 tripl e d c superv ivc nc ia quinq ucnal en los casos con lesion loca lizad a , ta nto en h ombrcs co m o en muj crcs, En t re las m u jcres c l ad cn ocarcino m a Y 1'1 ca rci no m a bronq u iolar terrnina l fu eron d os vcces ma s fr 'C UI' IItCS, a l pa so q uc en t re los hombres prcd ominaron cl carcinoma cp id c rJno ide Y 1'1 tipo oa t cell. EI ca rcino ma br onquiolar terminal localizad o, pr escnt o mejor es probabilidadcs d e su pe rv ivcn cia par a a mbo s sexos. E1 ca rci no ma ii po oat ce ll fue c l d e p ro nostIco monos Iuvor ab le. No h ubo d ifcrcnc ia n ot abl e en cuanto a SII superv ivencia en tre el ad cno carcinoma y 1'1 ca rcinoma c pi de r m o ide . Ent rc los cases loca lizados t ratados q u iru rgica men te la superv ivcncia fue cons istent e ment e m a yor ent re las m ujer es, Se cva lua n otras vari abl es d el p ron6sti co y la cfcc iividad p resen tc y fut u ra d e la s mcdidas prcvcnt ivas de ord cn prima rio y se cun d a ri o.
2 3
4
5
6 7 8
R EFERE:-:CES BOUCOT, K . R ., COOPER, D. A., W EISS, W . A:-> D C ARNAHAN, W. J.: " C iga re ttes, cou gh and can cer of th e lung " J A M A , 196: 985 , 1966 . Ca ncer Registrat ion an d Surviva l in California . Calif ornia Tumor R egistry, State of Ca lifornia Dept. of Pub. H ea lth , 1963, pp . 176 - 189 . CHRISTOPHERS ON, W. M. : " A re-evaluation of the significance of circulating cance r cells in the periphera l blood," from the text R ecent A d va1lces in th e Diagn osis of Canc er, Y ear Book Medi ca l Publisher s, Chica go, 1966 . COLLIER, F. C ., BLAK EM ORE, W . S ., K YLE, R . H ., E NTERLINE, H . T ., KIRDY, C . K . AND J OII:-> SON, J. : " Carci no ma of th e lun g: Iacturs whi ch influen ce five-year su rv iva l with special refere nce 10 blood vesse l in vasi on ," Ann . Surg., 146: 41 7, 195 7. CONNELLY, R . R ., C UTLER, S. J . AND BAYLIS, P.: " End results in cance r of th e lun g : comparison of ma le and female patients," J. Nat . Can cer I nst., 36:2 77 , 1966. C UTLE R, S. J. AND EDERER, F .: " M ax im um ut ilizati on of th e life table method in an al yzing survival," J . Chr onic ou., 8: 699, 1958 . . . EDER ER, F. : " A sim ple method for det ermllllng sta nda rd erro rs of surviva l rates, with tab les," ]. Chron, D is., 11: 632, 1960 . EDER ER, F., AXTELL, L. M . AND C UT LER, S. J.: "T he relative sur vival ra te : a sta tistica l methodo logy," Na t. Cancer l nst, Mon ogr ., 6: 101, 1961.
9 EIlERI;R, F . ANI> M ERSHEIMER, W . L.: " s d ifferences in th e su rv iva l of lu ng cance r p e " tien ts," Can cer, 15 : 42 5 , 1962. a10 EISE:->II ERG, H ., SIIA~IE S , J . ~l. , H OLLO'" • W. r.. ANI> BARRETT, H . S. : " C a nce r o f bron chus an d lu ng : Conn ecti cut, 19 35-195 9 ~ J. Ch ron , Dis., 17 : 10 33, 196'k ' . 11 FEINSTEIN, A. R . : " Symptomatic patt er ns b'I o ologic behavior, a nd progn osis in cancer o f' t.h lun g. Practica l appl ication of Boolean al ge b e a nd clin ica l ta xon omy," A nn . Int ern . M 2 1:27, 1961. " 12 G ILllERTSEN, V . A. : "X-ray examination t~lc chcst. An unsa tisfact o ry method of d er o f n on of ea rly lu n g ca nc er in asymptomatic ind~ vid ua ls,' J AMA , 188: 1082, 19 64 . 113 qll.IJ F. RTSI;:-:, V . A . : " The poten ti a lity for su viva l enha nce me n t by exped itious d et ec tio n r neop lastic di seas es," ( Ed . Ariel 1. 1\,[. ) Pro o f gress in Cl ini cal C anc er, G run~ and S;ratto eNew York , 1966 . n, 14 Hlm~I A N . D . L . AND C RITTENDEN M . : "D l' S triburi on uf pri mary lung carcino~na in rel tion to ti mc a s d et ermi ned by h istocheml j-,a -I . .. J• N at . Can cer I nst ., 27 : 12 27, 19 6- a. tee I1I11CS, I 15 I! UKILL, P. B. AND STERN, H.: " Adenoc a r' ~lIlom a of t!IC lu ng : h isto log ical fa ct ors affe c t.: mg pr ognosis. A stu d y of 38 patients with r secti on and 5-y ea r follow -up Canc er 15· 5 0~ 196 2. " . "T , 16 K RI;YIIERG, L . : " H isto logical lu ng ca nc er tYP e A mor ph ological an d b iological co rre l a tion~ ; A ct a Path . M icrobi al, S can d, ( Su p p!. ) 15 , ' 7, 1962. ' : 17 M E R s II EI ~m R , W. L . ANI> EDERER, F . : " E.nd resu lts eval ua tion of ca ncer of th e lung a n d b.run c h u~," in P roceedings of th e Fou rth JV a _ t io n al Can c e T Con feren ce, J. B. Lippincot.t. Ph iladel ph ia . 1960. • 18 SIII ;\IKIS, 1\1. B., CONNELLY, R . R ., MARCtJ S S. C . ANll C UTLER, S. J.: " Pneu m on ecto n l ' an d lol~ectomy in br on ch ogen ic ca rcin oma . co m par rson of end results of the O verholt a n d O chsner cl inic s," J . T ho r. Cardiouas. Surg H :503, 1962. " 19 STEELE, J. D . : "Carcinoma of th e lun g" ( t h e UC LA Int crd epartmcma l Conferen ce ), An n I ntern, M ed ., 6 '~ : 180 , 1966 . . 20 WATSON, W . L . : " Five-yea r su rvivors in lung ca nce r. A s t u d y of 3,0 73 cases," Am er. J R oent ge n. , 79 : 488, 1958 . . 2 1 WATSON, W. L. AND BERG, J . W.: " O a t Ce ll lu ng ca ncer," C II1lCer, 15 : 759 , 1962 . 2:! \ V t\ " S O N , W . L . ANlJ S~II TII , R . R . : " T crrn in n ] bro nchio la r or 'a lveola r ce ll' ca nce r of lu n g . rcport of 33 cases,' J A M A , 147 : 7, 1951. '
ti; .
eJa
tI
..t
For rep rints, please write: Dr. Watson , 3·10 Ea s t 77 th St ree t, New York 10021.
EVAL UAT ION OF FR EEZE DRIED KV El}, [ RE AG ENT sta ble. the advanta ges In clinica l pract ice ot an ettec_ t ive Irtx-ze-dr icd propa ratlon do not requ ire em pha_ sis . Th · posit ivity ra te In the pr esent st udy IncH_ ca tes Iha l rreeze-dr teu K ve lrn reagent is a po t ~n t test ma ter ia l in the diag nosis 0 1 sarcoidos is.
In active sarcoidosis freeze-dried Kvelm-t est mater lal gives derm al rea~ti ons of Identi ca[ macroscopic aPl'ea ranee to those produced by flu id reagen t. No " Ialse positive " reactions have so fa r been record ed with Irecze-drlcd antigen. Fre eze-dr ied antigen appear s to reta in its potency for long periods at room temperature .
While lIuid K vclrn -t es t substance Is remarkabl y
K'·NNWY. \VI . 1'. U . : " An eva lu at ion o f Freeze-d ried Kvc i rn rcagcm; " Brit. t. Dis. CluSl .• 6t: ·\0. 1967.