CancerOrthodoxyG. W. Taylor, M.D.

A great deal of recent writing on the subject of cancer questions or challenges niostof the basic assuniptions upon which orthodox niethods of management are based.@Vhilean unwillingness to accept dogma is a wholesome aspect of the scientific mind,

the substitution of a whole new unproved concept niay merely serve to confuse thepicture without offering any helpful contribution.

These new heresies have many superficial points of similarity with the religiousschisnis which characterized the Protestant Reformation. The challenge of dogma andrebellion from authority are the common points of dcparture. It should he remembered,however, that the orthodoxy of cancer ideology is based not upon divine revelationbut upon the accumulated observations and clinical experiences of generations of practitioners. Some of the newer promulgations, such as @biologicpredeterminism,― seemto parallel the doctrine of original sin. Some of the newer heretics seeni to bask in asmug certainty of righteousness comparable to the state of grace so eagerly sought bysonic of the earlier divines.

Unfortunately, sonic of these newer concepts appear to he wholly sterile and to leadto no fruitful amelioration of management. To sit down with the patient and deplorethe whole disease process will not cure cancer, nor even conifort the sufferer. The attitude of mind that accepts predeterminism is close to despair and decries the physician'sobligation to endeavor to better the situation.

The pernicious mischief of these heresies is that they are eagerly embraced by theincompetent and ignorant as justification for deviations from approved methods ofmanagement.To destroythephysician'sfaithinhiscapacitytomodifyeventsinbehalfof his patient, to deny him the belief that there is a way of salvation sanctioned byauthority, is to nullify his social usefulness. Until the heretics can enunciate a formulamore constructive than our present orthodoxies, only harm can result from dissemination of their ideas.

Reprinted from Surg., Gynec. & Obsi, 107:658, Nov., 1958.

[Reprinted by permission of aul/mor amid of Surgery, Gynecology and Obstetrics. Copyright,/958, by I/me Frammk/immH. Marlin Menmoria/ Foummdatiomm.Conmmemmls of Dr. ?slacdomma/d follow.See also Kotimm. P.: Cammcer /meterodoxy. Surg., Gynec. & Obst, 108:6/8-6/9, May, 1959: andHammond, E. C.: Time possibility of improvimig cammcer cure rates at I/me preseimt tinme. Cancer10:581-586, May-f umme,1957.—ED.]

Heterodoxy in CancerTherapyIan Macdonald, M.D.

Although the editorial by Grantley W.Taylor repeatedly refers to “¿�newheresies―in the plural, he identified (also plurally)only that form of heresy for which Icoined the expression “¿�biologicpredeterminism― in 1950.' This belated, but notunemphatic denunciation of our undistinguished efforts toward a better understanding of the natural history of cancer we regard as the most signal honor which has

From the Departmnent of Surgery, UniversIty ofSouthern California, School of Medicine, Los Angeles, California.

yet been accorded our particular varietyof heterodoxy. For so stentorian a protestfrom the heart of New England may, perhaps, indicate that such intellectual flummery has made its insidious entry into Boston as an eight-year-old backwash from thefrenetic frontier of Southern California,ordinarily regarded h@'many Bostonians asan academically arid area.

If this conjectural exercise is of any validity, the ire of Dr. Taylor is entirely comprehensible, but offers no contraindication to as vigorous a counterattack as the

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writercan provide,and allthemore sofrom so effective a vantage point as thepages of CA.iftheattitudesexpressedby Dr.Taylor

were correct I would be exposed as an utterly incompetent investigator and a charlatan of sorts, with a distinctly low level ofperception to boot. Fortunately, any tangible issues raised are uniformly erroneous,while the intangible and even emotionalphrasings speak for a measure of insecurity of the orthodoxian concerning his orthodoxy. I hold no particular affection forthe implications of predcterminism in disease, but the evidence is sufficiently convincing as to demand recognition.

In the first paragraph, the key word is“¿�unproved,―as applied to predeterminism.From a broad viewpoint, the evidencewhich was presented in the original articles in 1950' and 19512 produced a concept which was synoptically expressed asfollows: “¿�thebalance of power betweenneoplastic and reactive influences in thehost has been established in the preclinical phase of the process, and in a clinicalsense this concept may be expressed asthat of biological predeterminism.―2 In arestatement of this approach, in 1958,based on further evidence from largergroupsof patientswithvarioustypesofcancer, and viewed in relation to end results of treatment, one of the conclusionswas: “¿�theoutcome of the preclinical struggle for power, between a developing neoplasm and the enigmatic defensive reactions of the host, is of greater prognosticimportance than the time or type of treatment.―4

The original supporting data were thoseof duration and dimension of the primaryneoplasm, correlated with local spread, orcurability, or both, for carcinoma ofbreast, stomach, colon, uterine cervix andsarconia of bone. Of these, only for thecervix was there a consistent relationshipbetween duration and curability, hut hereit was of such critical importance as toemphasize the extreme importance oftreatment instituted one month or lessafter the onset of symptoms.

Gastric carcinoma and bone sarcoma,by contrast, were found to have an un

favorable natural history, as indicated bya direct ratio of duration of symptoms tocurability, i.e., increasing periods of delay,trom onset of symptoms to definitive treatment, were attended by comparable increments both in resectability and curability.For gastric carcinoma, the data were obtained from a series of 6242 patients atthe Mayo Clinic, and the more favorablestatus with increasing periods of delay appeared in the 195 1 article2 in tabular form:

GASTRIC CARCINOMA

Delay Resectabil. 5-yr. survivorsinterval % %

0-3 months 35.8 20.8

7-1 1 months 42.5 23.2

1-2 years 45.0

53.9

The biology of mammary carcinoma ismuch niore variegated than any of thepreceding neoplasms, as will be outlinedin a more suitable frame of reference,below.

In Dr. Taylor's second paragraph, ananalogy is drawn between early Protestantsects and our refusal to accept a uniformfaith in “¿�early―treatment of cancer, with“¿�rebellionfroni authority― as a commonpoint of departure. \Ve (the heretics) areadvised to heed the orthodoxy based on“¿�accumulatedobservations and clinical experiences of generations of practitioners.'This rhetorical statement epitomizes theperpetuation of error with which the history of medicine is replete. But in this instance a whole body of well-meant propaganda has been built around an oversimplification of a complex problem. Only byan objective study of various forms of cancer were the fallacies and exceptions to thetraditional attitudes exposed, and with nohelpful spark of “¿�divinerevelation.― Ourearliest approach to the natural history ofcancer was not undertaken with any preconceived concepts. It was a realization ofthe frequent contradictions to the traditionally accepted value of “¿�earliness―in

27.2

38.53-4 years

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time and size which prompted me to attempt an evaluation of their real importance, an effort which began in 1946. Asearch of the literature was singularly unrewarding; it was common for authors topreface their presentation of end resultswith lamentations over the failure of patients to present themselves for treatment“¿�early―in the disease, but to find a correlation of end results with duration or tumorsizewasa rarity.Everyonehadbeengenuflecting at the shrine of “¿�earlydiagnosis,―but none of its votaries made any effort tosurround the shrine with good, unassailable walls of documentary proof.

Even if I ignore the more contumeliousand derisive language, Taylor betrays asterility of thought by implying that the“¿�heretic―lacks both sensitivity and intelligence when he makes the absurd assumption that one would “¿�sitdown with the patient and deplore the whole disease process―!I have never suggested that the trueperspective of the curability of cancershouldbeanypartofpubliceducation,andIshallsuggestthepossibilitythatpatientsfor whose care I am responsible have asfirma beliefintheirprospectofcureasdothose who are cared for by my distinguished critic.

More important, and just as inaccurate,is the statement that “¿�predeterminism isclose to despair and decries the physician'sobligation to endeavor to better the situation.― Let the words Dr. Taylor has notread, or understood, speak for themselves.

An appreciablefractionof cancerswhich by clinical standards are late represent biologically dilatory processessusceptible of cure.

This sort of evidence is indication fora radical change in the clinician's philosophy of cancer therapy. Rigid ideasof prognosis in terms of duration anddimension should be abandoned in favorof an attempt to evaluate the biologicalpotential of a neoplasm in an individualhost. Tangible factors presently available for such an evaluation are admittedly imperfect, but in some forms ofcancer the suni of evidence provided intheir rate of growth and gross andhistologic features constitutes reason

ably accurate information.2Those who regard predeterminism as

an expression of therapeutic futilitymust reject entirely the inexorability ofnatural selection in cancer. Some typesof cancer do have a natural historywhich generally confornis to the traditional doctrine that curability is directlyrelated to the “¿�earliness―of diagnosis,the‘¿�Immediacy―and theeffectivenessof treatment. These are the forms ofcancer in which both the degree of spaceoccupation by the priniary neoplasm,and the anatomic extent of regional anddistant metastasis, is a function ofchronologic duration. Such is the natural history of squamous carcinomas ofthe skin, lip and uterine cervix, whichrepresent a mid-zone in the spectrum ofbiologic predeterminisni.4

The futility, or even the unfavorableeffects of surgical treatment in someforms of cancer, should not obscure thecurative and palliative accomplishmentsof adequate, meticulous, operative procedures . . . responsible for the niajorshare of present rates of clinical control.4

Indicated (in a figure) is an estimateddistribution of 100 patients (with breastcarcinonia) based on factors inherent inbiologic predeterminism (and for whichmultiple sources of evidence have beenshown). Twenty individuals would havea favorable result, usually curative ineffect, even with something short ofideal treatment, at any time up to threeyears after onset. Forty-five to 50 ofeach 100 have neoplasms of high growthpotential and inadequate host-resistance, in whom regional or distant metastasis is established before the primarylesion is clinically apparent. In the remaining 30, there should be the relationship between time, space occupationand metastasis implied in the traditionalconcept of “¿�early―diagnosis.* For1/zese 30 women, I/me extent of timeir disease is indeed a function of time. It is

for this group I/mat not only prompt, butadeqmiate, effective treat mnent may meanI/medifference between cure and failure,between life and death.3

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The final stone thrown at predeterminism is one I have become expert in dodging; expressed by less caustic critics thanTaylor, the pitch is a gentle appeal to reason, i.e., to forsake the “¿�partyline― ofearly diagnosis and early treatment is toconfuse the family physician, who willthen become entirely pessimistic. Further,it is argued, this concept of variability inthe potential of cancer in the individual istoo difficult for the average physician tograsp. There are several answers to this,but the most important deserves great emphasis: the truth as it is known, or as itseems to the qualified observer, is the mosteffective stimulus of interest and the bestpreventive against apathy for the professional audience. Many thoughtful physicians who had never operated upon a patient with cancer were well aware of thefallacies inherent in the oft-repeated message of “¿�earliness―long before the presentcrop of “¿�heretics―were being heard. Isuggest that the Boston specialist exhibitsa pose of superiority toward the familyphysician which is hardly warranted in theface of his own failure to acquire any vestige of the implication of predeterminism.My own faith in the “¿�averagephysician―is such that I reject the notion that he actseffectively only when his beliefs are sanctioned by “¿�authority―;his social usefulnesswill be increased by any challenge to authoritarian concepts which induces newthought, renewed observation and personalefforts at evaluation of old vs. new ideas.Many general practitioners have becomekeen observers of the natural history ofcancer as seen in their own practice,through the stimulation provided by nontraditional ideas; from such reappraisalsmany of them have come to understand

the limited importance of time and spaceoccupation in cancer, to appreciate thesignificance of the individualization ofeach patient. With such attitudes becoming more prevalent, usually without benefitof any polysyllabic verbalizations such aspredeterminism, there has developed anincreasing awareness of the importance ofthe consultative process toward selectionof the niost promising therapeutic methods, directed either at cure or palliation.Thus the shrugging off of outworn orthodoxy has resulted in more constructive attitudes, to the benefit of the patient.

As to the incompetent and ignorantwho may embrace eagerly our heresies tojustify their deviations froni “¿�approvedmethods,― I must remind the editorialistthat I use the same “¿�approvedmethods,―though in a less historic milieu, but I donot apply any set of rules of “¿�inoperability― to the individual patient. I have aslogan, too, which provides for an occasional patient a chance for cure, or longterni palliation, that he niight not havebeen afforded in areas where the theme of“¿�earliness―is dominant. This slogan pointsup the insubstantial nature of such academic differences as gave rise to this prolixcommunication, for I ani sure that GrantIcyTaylorwillagreewiththisitemofmyfaith: “¿�LateCancer May Also Be Curable.―

His prose creates most grievous domihtsA mong the medical classesHis /meterodoxy is decriedAs dangerous for t/me massesHis major I/moug/mts are classifiedA mong the noxious gases.

P/mysician.s awake!

(paraphrased from Lawrence Durrell)

*j.romn I/mis ommemay derive an estimated, idealistic or utopian “¿�cure―rate of 55 per cemmtalfime @‘¿�ears.T/mishas 10 per cemztbetter t/ma?mour previous, best estimate, due to a larger sample,694, of ms'/mic/ma/mnost JO per cent of paliemmls /mad conme to radical nmastectomy ms'/memmI/meprimarylesiorm was 1.0 cm. or less in diamneter; of I/misgroup only 40 per cent /mad microscopic em'idermceof spread to axi/lary nodes. T/mus, ste commtrihuted valid support to I/me relative value of diagimosis at an early phase, w/mic/mis more 1/maimcan be said for 1/mose ms/mooveremnp/masize its itimportammc'e, bitt rarely lake I/me trouble to determnimme to mi/mat degree I/me facts fit 1/meir slogaims.

References1. Macdonald, 1.: The factor of early treatment in biology of mammary carcinonma. In Proceedings ofthe curability of Izuman cancer. Acta Unio internal. the Third National Cancer Confereimce. P/miladelphmia.contra cancrum 6:1396-1402, 1950. J. P. Lippincotl Co. 1957; pp. 87-95.2. Macdonald, 1.: BIological predeterminisin in hu- 4. Macdonald, 1,: The individual basis of biologicman cancer, Surg., Gynec. & Obst, 92:443-452, 1951. variability in cancer. Surg., Gynec. & Obsi. 106:227-3. Macdonald, 1.: indications of ihe fundamental 229, 1958.

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