Tuesday, September 9, 2014

Historical Contribution: 1950, Further Investigations into Hormonal Relationship of Prostate Cancer


H. Brendler, W. E. Chase and W. W. Scott. Prostatic Cancer - Further Investigation of Hormonal Relationships Archives of Surgery. 1950 61: 433-440

William Wallace Scott, MD
Huggins and Hodges seminal work that defined the hormonal nature of prostate cancer was published in 1941.[1] The following decade saw a surge in the enthusiastic investigation of the relationship between androgens (i.e. testosterone) and prostate cancer. Based on the work by Huggins and Hodges, it was believed that prostate cancer was dependent on androgens to grow and spread. Cases of progressive metastatic disease after castration (by orchiectomy or medications) were, therefore, believed to occur as a result of extradonadal androgens – namely from the adrenal. This was refuted in a study by Huggins and William Wallace Scott (2nd Director of Urology at the Brady Urological Institute), where a patient who was previously castrated for prostate cancer, also underwent bilateral adrenalectomy and experienced continued progression of disease despite removal of all endogenous androgen.

Without knowledge of the androgen receptor and castration-resistant mechanisms, researchers at the Brady Urological Institute sought to investigate the relationship between androgens and prostate cancer by treating three men with advanced cancer with testosterone proprionate and reported their results in this publication.

There are a number of interesting clinical findings from the cases:
  • Two had bone metastases visible on x-ray (roentgenogram), both diffusely throughout the skeleton and involving the sternum.
  • With testosterone injections, hemoglobin improved and acid phosphatase decreased.
  • Interestingly, pain improved in the one patient with bone pain, bone lesions stabilized or improved in all patients – no patient had progression during follow-up.
  • The two patients with bone metastases died within 100 days of starting treatment.
  • The patient without bone metastases had no changed in acid or alkaline phosphatase, and had dramatic improvement of his voiding symptoms with diethylstilbestrol.
The clinical course and treatment of each patient is detailed in the figures.

During this time period, the understanding of hormones and breast cancer was also expanding. In breast cancer, it was believed that androgens were related to osseous metastases while estrogens affected soft tissue disease. Through extension, Brendler, Chase and Scott hypothesize that androgens may play a role in the bone metastases so common in prostate cancer.

To read the entire manuscript: follow the link above, visit the Centennial Website or here.

HISTORICAL CONTRIBUTIONS highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years.  As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years.  In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field.  We hope you enjoy! 

[1] 1. Huggins, C., and Hodges, C. V.: Studies on Prostatic Cancer: I. The Effect of Castration, of Estrogen and of Androgen Injection on Serum Phosphatases in Metastatic Carcinoma of the Prostate, Cancer Research 1:293, 1941.

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