CANCER EPIDEMIOLOGY AND T H E CLINICIAN: SUMMATION SPEECH

BRIAN MACMAHON, MD

IRST, I WOULD LIKE TO CONGRATULATE THE F organizers of this symposium, and the speakers, for a tremendously stimulating set of presentations.

I do not propose to attempt to summarize the conference. Those who want such a summary will have to wait until the published pro- ceedings. Rather I would like to give my view of the major objectives of the conference, and to what extent it succeeded.

In his opening remarks, Dr. Lessner indicated that, in the minds of the organizers, the confer- ence had two objectives: 1) to review selected genetic and environmental factors in the etiology of cancer, and place them in perspective; and 2 ) to facilitate interchange between epidemiolog- ists and investigators in clinical medicine.

Attainment of the first objective may be sum- marily granted. When clinical trials, the long- term follow-up of cancer patients, the possibility that some cancers are infectious, the roles of occupation, diet, genes, hormones and radi- ation, and the morass of the etiology of cervical cancer have all been touched upon, then one has indeed reviewed the major growth points in can- cer epidemiology.

I t is the second of Dr. Lessner’s objectives to which I would like to give most attention, for it is the attainment of this objective which will have the greatest impact on the future of both epide- miology and clinical medicine.

In this conference the epidmiologic fraternity was given an opportunity to show its wares and attempt to convince the clinical community that what epidemiologists are doing is worth while and, beyond that, of interest to clinicians specifi- cally. There are several reasons why this is of great importance for epidemiologists. The most crass is that, at this point in the development of epidemiology, its practitioners are almost

Presented at the National Cancer Institute Conference on Cancer Epidemiology and the Clinician, Boston, Mass., Oc- tober 23-25, 1975.

From the Harvard School of Public Health, Department of Epidemiology, Boston, Mass. 021 15.

Address for reprints: Brian MacMahon, MU, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115.

Received for publication August 26, 1976.

wholly dependent on clinicians for access to their most important research material- patients. One still sees-primarily in countries where epidemiology is less developed than it is in the United States-epidemiologic in- vestigators completely divorced from clinical medicine pondering published vital statistics and similar material in attempts to develop or test etiologic hypotheses. While such ponderings still, occasionally, lead to useful observations, routine sources have, by and large, been gone over so many times that new insights from them are unusual. We need access to the one person who, of all people, knows more about his or her life experiences than anyone else-the patient.

Second, I do not believe that as a group, epi- demiologists are in the game for kicks. In- tellectual challenge there may be in the field- and it is a decided asset-but a more important motivation is the hope of identifying environ- mental factors, the modification of which may prevent illness. In 1636, John Graunt, in- troducing his Natural and Political Observations made upon the Bi l l s of Mortality, wrote:

Moreover, finding some Truths, and not commonly-believed Opinions, to arise from my Meditations upon these neglected Pa- pers, I proceeded further, to consider what benefit the knowledge of the same would bring to the World; that I might not engage myself in idle, and useless Speculations, but . . . present the World with some real fruit from those ayrie Blossoms.

What use to grow fruit if nobody eats it? And where should we find a better market for our produce than among those whose profession is maintaining the health of the community and who see most directly the consequences of our failure to prevent illness?

The third reason for bothering about what the clinician thinks about epidemiology and epi- demiologists is the historical record of the fre- quency with which an alert clinician has opened up a pathway of productive epidemiologic in- vestigation. Pott on scrota1 cancer, Snow on cholera, Murphy on congenital malformations,

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No. 4 SUMMATION SPEECH MacMahon 1921

Gregg on prenatal rubella and Lenz and McBride on thalidomide are only a few exam- ples. The quantitative estimates of the size of the effects of causative agents made by these and other clinicians have frequently been in error, but the association was made-the door opened-by them. Quantitative estimates of risk cannot be made until we know which causes to link with which effects. Surely we want clini- cians to continue to be alert to possibly mean- ingful associations and to know that there is a profession whose specialty is the deeper explora- tion and quantification of associations between environment and disease.

As an illustration of the extreme point of view regarding the inter-dependence of epidemiology and clinical medicine, I could point to the situa- tion in the Soviet Union where, while cancer epidemiology is a recognized-and apparently even valued-activity, there are virtually no can- cer epidemiologists. Epidemiologic studies are conducted by physicians who are, first and fore- most, clinicians. This situation appears not to be the result of shortage of medical manpower but is in fact justified to visitors with the argument that, in order to study the epidemiology of an illness one must first know about the illness and the person who knows about illness is the clini- cian. It is an interesting argument, although it appears not to be applied to pathologists, bio- chemists and virologists who also are concerned with the causes of disease. The consequences of its application to epidemiology is that, while the Soviet epidemiologists may indeed know more about the clinical aspects of the illness they are studying than their American counterparts, they know considerably less about modern epidemio- logic techniques-particularly those relevant to analysis of large bodies of data-and their over- all efforts suffer on that account. There is, I believe, a strong case for a n intermediate posi- tion.

Has this conference made such a case? I be- lieve it has at several levels, four of which I will summarize briefly. One is the level of concern of matters which are of interest to all professions dealing with the health-of the community. The second deals with matters of special interest to the clinician; that is, information he can use in his actual clinical practice. The third deals with studies from which data relevant to both etiology and therapy are derived. And fourth, there have been described methodologies devel- oped in epidemiologic studies which have appli- cation to clinically oriented problems.

In the first category-matters of general inter-

est to all who are concerned with the health of the community-I would place most of the pa- pers we have heard on the problem of occupa- tion and cancer, diet and cancer and the very vexing problem of viruses and cancer of the cer- vix. These are problems that seem to have little immediate clinical relevance, but which clearly would have major health implications if they were resolved. These are problems in which epidemiology seems to have an important though by no means exclusive role to play.

With respect to matters of special interest to the clinician, this has been the focus of the con- ference, and it is the area in which we have heard the most examples. We have heard, for example, of the possible infectious nature of Hodgkin’s disease, and perhaps leukemia as well. I know of no other recent epidemiological observation that has caused more distress among those in actual contact with patients than the reports suggesting that Hodgkin’s dis- ease may be contagious. I recall writing an edi- torial for the N e w England Journal of Medicine on one of the studies of the Albany group published in that journal. After stating the pros and cons in proper non-commital academic fashion, I ended with the thought that Dr. Vianna and his colleagues have identified a problem that needs further investigating. It was now up to the rest of us to investigate it. Our local radiotherapist told me that he liked my editorial very much-espe- cially the last sentence! In my view, there is no issue in the cancer field that is of more immedi- ate practical concern to the clinicians than to resolve the question of whether Hodgkin’s dis- ease is or is not contagious. We have also heard about the health effects of oral contraceptives, a matter of obvious significance to the clinician who prescribes such agents. We have heard a review of the effects of estrogens given at or after menopause, a review notable for its indication of the lack of information available on this subject. We have heard about the discovery of the terato- genic effects of stilbestrol in utero, which occa- sioned the same stimulus to further research as did the observations of Gregg on congenital ru- bella and congenital malformation. We have heard of several studies of the long-term effects of medical therapies for various categories of patients, particularly children with cancer. All these studies have direct relevance to clinical practice.

Arbitrarily I would also classify in this cate- gory some of the community applications, such as the cervical cancer screening programs that both provide epidemiologic information and

1922 CANCER April Supplement 1977 Vol. 39

might, at the same time, give the clinician some idea about the patients who are escaping screen- ing in the community and to whom he should devote particular attention in his practice.

And lastly, we have heard about methods de- veloped for epidemiologic studies that have ap- plication to clinical problems. It was recom- mended that a s tandard and simple occupational history should be included in clini- cal records. Such a history would identify new associations. But it would also be relevant to the care of individual patients; perhaps not so much to their clinical care but to their related social and financial concerns. Second, there has been in recent years a very rapid development of sta-

tistical methods in observational studies, devel- oped primarily for the analysis of confounding in observational studies but relevant also to the analysis of experimental clinical trials. I would suggest that those methods are also relevant to observational studies that have primarily a clini- cal objective. For example, observational as dis- tinct from experimental studies of the efficacy of therapy, and the evaluation of immunologic and other cancer screening tests.

I would like to repeat my congratulations to the organizers of the conference and express my own opinion that it has greatly strengthened the interdependence of epidemiology and clinical medicine.