PROSTATE CANCER: A BRIEF HISTORY AND THE DISCOVERY OF HORMONAL ABLATION TREATMENT

To the Editor. The author is to be congratulated for this outstanding review of the historical aspects of prostate cancer and its treatment. Starting with the discovery by John Hunter at the end of the 18th century, castration was subsequently applied for the treatment of benign prostatic hyperplasia in the second half of the 19th century. Nevertheless, the transfer of this concept to malignant tumors of the prostate was not undertaken until the 1930s. This delay is astonishing considering the fact that the Scottish gynecologist George Thomas Beatson had already introduced bilateral oophorectomy for treating metastatic breast cancer as early as 1895. His case was the subject of the first published report of a successful endocrine manipulation of a human malignancy. However, gynecologists would ignore this landmark procedure until the introduction of radiooophorectomy in the 1930s.1 To enlighten the discussion on the priority of introducing hormonal therapy for prostate cancer, Lytton cites the 2 unsuccessful cases reported by Hugh H. Young in 1936.2 A close look at this reference reveals that therapeutic castration in these 2 patients was undertaken accidentally rather than for oncological reasons. The first patient suffered from prostatic obstruction, and the surgeon, not knowing of the cancer, “performed castration, which was then in vogue, in order to produce an atrophy of the enlarged prostate.” In the second case “the diagnosis of carcinoma was evident,” and the patient complained of severe pain in the rectum, buttocks and limbs. Again, “castration was performed with the hope that some change in the prostate, which might bring about relief of the rectal pain, might follow.” No further ideas on endocrine mechanisms were mentioned by Young, and systemic therapy for metastatic disease in prostate cancer was therefore not suggested in his report. More surprising is a report by Edward L. Keyes and Russell S. Ferguson of New York, who had performed radio-orchiectomy in several patients since 1932 and published the following statement in 1936: “Extension of the life of the patient in comfort, even in the face of widespread metastatic disease, may be accomplished by taking advantage of our present theoretical knowledge of the physiology of growth of neoplastic prostatic epithelium. To this end we have combined roentgen castration with local irradiation to good effect in a number of cases. The apparent influence of the castration is to decrease the rate of growth and even in some instances to arrest the growth entirely in both the primary tumor and in the metastatic lesions of the disease.”3 In 1941 several reports of systemic therapy for prostate cancer, including radio-orchiectomy (A. D. Munger), surgical castration (A. Randall) and estrogen administration (J. G. Strohm, W. P. Herbst, R. D. Herrold and W. M. Kearns), were presented at meetings of the Chicago Urological Society and the American Urological Association, parallel to the first presentations of Huggins, or were published in journals.4 In conclusion, one must realize that the initial impetus for endocrine treatment of prostate cancer was given by several authors at the same time, who should therefore all be part of the medicohistorical record. Acknowledgment of their contributions does not minimize the achievements of Charles Huggins, who was the outstanding scientist among this group, who conducted thorough and continuous research on hormonal treatment of cancer during the ensuing decades, and who therefore was finally honored with the Nobel Prize in 1966.1, 4