Once injectable agents were proven to lower testosterone levels, they became the preferred treatment among patients and their treatment teams.
Leonard G. Gomella, MD
The Bernard W. Godwin Jr. Professor of Prostate Cancer Chairman, Department of Urology Director, Clinical Affairs Kimmel Cancer Center Thomas Jefferson University Philadelphia, PA
For the better part of the 20th century, urologists and oncologists have understood the link between androgen levels, specifically testosterone levels, and their ability to stimulate prostate cancer cells. Until the 1980s, surgical castration was thought to be the most effective method to lower androgen levels. However, once injectable agents were proven to lower testosterone levels, they became the preferred treatment among patients and their treatment teams, even if testosterone levels were not as low as what could be achieved by surgical castration.
But just how low do testosterone levels need to be in order to halt the progression of prostate cancer? For many years, a level of 50 ng/dL was considered appropriate to halt the progression of the disease and prevent the development of castration-resistant prostate cancer. However, studies have suggested that lower testosterone levels are associated with prolonged survival, and that levels between 20 and 50 ng/dL led to worse outcomes.
“Although 50 is the official number, now we’re starting to say, ‘Well, maybe 50 is too high,’” said Leonard J. Gomella, MD.
Gomella and colleagues conducted an exhaustive literature review to see whether they could arrive at a new consensus on what the castration level for testosterone should be. The review—published in November in the British Journal of Urology International—examined studies that observed hormonal changes as a result of androgen deprivation therapy (ADT), the use of testosterone measurement, the efficacy of intermittent androgen deprivation (IAD), the underlying mechanisms of castration resistance, and novel treatments for castration-resistant prostate cancer.
The literature review suggested that lower testosterone levels appear to lead to better outcomes almost across the board. However, the authors were not able to arrive at a uniform consensus because many of the key studies in the analysis were retrospective.
Despite that limitation, Gomella said that the studies are hypothesis-generating, suggesting the need for prospective studies. Another limitation, according to Gomella, was the quality of blood tests that measured testosterone levels, as well as the timing of tests. Although the FDA recommends periodic testing of testosterone levels, there is no standard of care, and urologists and oncologists debate just how frequently testosterone levels should be measured.
“Hopefully, the Endocrine Society and the AUA and other groups are going to standardize and optimize what the best blood test is for measuring testosterone,” Gomella said. “Then, perhaps, we can bring some more standardization in this area of what testosterone levels are in the management of patients with prostate cancer.”
Djavan B, Eastham J, Gomella L, et al. Testosterone in prostate cancer: The Bethesda consensus. BJU Int. Published online ahead of print November 30, 2011. doi: 10.1111/j.1464-410X.2011.10719.x.