Androgen Depletion Therapy for Prostate Cancer May Make it Worse

Okay, guys, there is one basic rule with prostate cancer - if they want to use androgen depletion therapy (ADT) to eliminate your testosterone in the (false) belief that it will save your life, you need to find another doctor. Period. This article explains examines how ADT can actually INCREASE your risk of developing an aggressive form of the cancer.

Key point:

"Stretching our data even further, these findings suggest that as men age and their testosterone levels decrease, loss of testosterone might actually encourage indolent prostate tumors to become more aggressive," Roberts said. "This suggests that testosterone supplements might be a good thing for the prostate, even though current wisdom suggests the opposite."

If you have an aggressive form of prostate cancer, it will already have metastasized to bone by the time you receive ADT (it happens very early in the process) - and then with ADT you will lose sex drive, muscle mass, and bone density (not to mention developing cholesterol issues, depression, and potential heart disease). Once it gets into the bone, your chances of survival are lower, anyway - so why die impotent and depressed?

Another important issue is that ADT - when it works - only works for a couple of months, while the PCa is androgen-dependent. Eventually, it will become androgen-independent and things get worse form there.

The upshot of this research is that using ADT in men who are in the early stages of benign prostate hypertrophy (BPH) or high-grade prostatic intraepithelial neoplasia, a prostate abnormality that is thought to lead to prostate cancer, should not be deprived of testosterone because it raises the risk of developing a high-grade, aggressive form of the cancer - the opposite of what they intend with this treatment,

The numbers vary, but only around 10% of PCa is aggressive, and the death rate is down to around 3-6% for PCa overall (depending on whose numbers you read). Here is one set of stats, which is a little scary for guys my age (45), who entering the risk years:

Given current screening trends, it is estimated that 16.2% (1 in 6) of American men alive today will be diagnosed with the disease and approximately 3% (1 in 33) will die of the disease (Brawley 2012).

Here is the new research:

Preventing Prostate Cancer Through Androgen Deprivation May Have Harmful Effects

24 December 2012

The use of androgen deprivation therapies to prevent precancerous prostate abnormalities developing into aggressive prostate cancer may have adverse effects in men with precancers with specific genetic alterations, according to data from a preclinical study recently published in Cancer Discovery, a journal of the American Association for Cancer Research.

"The growth and survival of prostate cancer cells are very dependent on signals that the cancer cells receive from a group of hormones, called androgens, which includes testosterone," said Thomas R. Roberts, Ph.D., co-chair of the Department of Cancer Biology at the Dana-Farber Cancer Institute and professor of biological chemistry and molecular pharmacology at Harvard Medical School in Boston, Mass.

Previous findings from two major randomized, placebo-controlled prostate cancer chemoprevention trials revealed that androgen deprivation therapy reduced the overall risk for low-grade prostate cancer. However, both trials also revealed a high cumulative risk for high-grade prostate cancers that has caused concern among experts.

High-grade prostatic intraepithelial neoplasia is a prostate abnormality that is considered to be a major precursor to prostate cancer. Loss of the tumor suppressor PTEN is detected in 9 to 45 percent of clinical cases.

Using a mouse model of PTEN-driven high-grade prostatic intraepithelial neoplasia, Roberts and his colleagues investigated whether surgical or chemical androgen deprivation could prevent the cancer precursor from progressing to more aggressive disease.

"When we castrated the animals, we thought the tumors would shrink and they did initially," Roberts said. "However, they then grew back and became invasive."

The results of this preclinical study suggest that prophylactic reduction of the most active form of androgen, or blocking androgen receptor function, might have unintended consequences in some men.

"Stretching our data even further, these findings suggest that as men age and their testosterone levels decrease, loss of testosterone might actually encourage indolent prostate tumors to become more aggressive," Roberts said. "This suggests that testosterone supplements might be a good thing for the prostate, even though current wisdom suggests the opposite."

Roberts noted that these results should be interpreted with caution because the prostate glands of mice are different from their human counterparts. More data on human tumors are needed to evaluate whether the data from this mouse study are applicable to men.

Source: The American Association of Cancer Research

Citation:
Brawley, OW. (2012). "Prostate cancer epidemiology in the United States." World J Urol 30(2): 195-200.