There is a longstanding belief that prostate cancer may be fueled by the presence of male hormones (androgens), particularly testosterone and dihydrotestosterone (DHT). A supporting factor for this belief is the phenomenon that occurs when men with recurrent prostate cancer are treated with Androgen Deprivation Therapy (ADT, also called hormone blockade). There are two different but related types of ADT. One interferes with the body’s production of testosterone, and the other interferes with the cancer cells’ ability to “uptake” male hormones. ADT is effective in stopping the cancer in its tracks for a period of time.[i] This halt in cancer progression can be monitored by PSA tests, prostate biopsy, and/or imaging using multiparametric MRI. (Note that hormone blockade is not curative; over time, the cancer becomes resistant to its effects, which is then called hormone refractory prostate cancer.) Hormone blockade tends to reduce the size of the prostate gland, but there are side effects particular to the various medications that are prescribed.
First, I want to explain the most common medications that are used as a blockade strategy against prostate cancer:
Luteinizing hormone-releasing hormone analogs (LHRH) – The trade names for this class of drugs are Lupron, Eligard, Zoladex, Trelstar and Vantas. Use of these drugs is called chemical castration, because they stop the testicles from producing testosterone; if patients are given the choice between surgical castration (orchiectomy or removal of the testicles) vs. chemical castration, they usually choose the drugs because the effects are reversible if they discontinue use. These medications are injected or placed as small implants under the skin. Depending on the drug used, they are given anywhere from once a month up to once a year. Side effects may include reduced sexual desire, impotence, hot flashes, mood swings/depression, breast tenderness, anemia, loss of muscle mass, weight gain, and fatigue. Use of these medications can also contribute to loss of bone density and shrinking of the testicles and penis.
Anti-androgens – The trade names for these drugs are Casodex, Eulexin and Nilandron. Prostate cancer cells have receptors that take up androgens. These drugs “trick” the cancer cells by mimicking androgens, so they are taken up by the receptors instead of the body’s natural testosterone. However, they do not feed the cancer in the same way that androgens appear to. Side effects may be similar to LHRH drugs, except for sexual side effects. Thus, anti-androgens may be tried as a first line of hormone blockade, before LHRH.
Combined androgen blockade (CAB) – If either LHRH or anti-androgens alone begin to lose effectiveness, they may be given together at the same time, called Combined Androgen Blockade. In this case, all side effects are possible; in addition, diarrhea, nausea and liver problems may occur.
Triple androgen blockade (TAB) – A drug called a 5-alpha reductase inhibitor (trade names Proscar and Avodart) may boost the effect of CAB, though the research is somewhat contradictory on whether this benefit actually occurs.
When is hormone blockade indicated? There is no definitive agreement on this. Some physicians will prescribe it for patients with less than 10 years of life expectancy, especially if they do not want or can’t have surgery or radiation, and are able to tolerate the side effects. There is also some thought that men with early stage, low risk prostate cancer could use ADT as a form of watchful waiting, but this idea is not generally accepted as there is a risk of missing a treatment window, especially if the hormone blockade is masking an advance in disease aggression. In addition, younger men who are sexually active do not want the diminished libido that is a common side effect of hormone blockade, especially with LHRH or combined androgen blockade.
The most common use of hormone blockade is in patients who have had whole-gland treatment but their PSA is now starting to rise. If testing and diagnosis reveal cancer recurrence, ADT is a good strategy as it can add years to cancer control. Research is ongoing as to the best time to start, whether to start with a combined approach or not, and whether intermittent hormone blockade is a better approach than constant use.
ADT may also be prescribed prior to prostate cancer treatment, especially if the patient has an enlarged gland. Shrinking the prostate gland can make the therapy easier to administer in a comprehensive manner, thereby increasing the effectiveness of the treatment.
Along those lines, another growing application is to prescribe ADT in conjunction with some form of radiation therapy for patients with intermediate-to-high risk prostate cancer, or locally advanced disease that is considered not amenable to a localized whole-gland therapy. For radiation to be effective against a high Gleason grade, the dose would have to be so large that the risk of long-term side effects would increase. Because ADT both shrinks the prostate, and also temporarily halts progression, radiation patients who have concurrent ADT tend to survive longer than those who don’t.[ii]
On the other hand, patients with a rising PSA or other evidence of new disease after a focal treatment should consider a second focal treatment or other definitive approach. For this group, hormone blockade would not be the strategy of choice.
To sum up, there is a place for hormone blockade in patients with recurrent prostate cancer who are no longer candidates for a local salvage treatment. But we must also question the assumption that supplementing testosterone is contraindicated for men with early stage, low-risk prostate cancer.
[i] Turner B, Drudge-Coates L. Phramacological treatment of patients with advanced prostate cancer. Nurs Stand. 2014 Feb 5;28(23):44-8.
[ii] Roach M III. Current trends for the use of the androgen deprivation therapy in conjunction with radiotherapy for patients with unfavorable intermediate-risk, high-risk, localized, and locally advanced prostate cancer. Cancer. 2014 Mar 3. Doi: 10.1002/cncr.28494. [Epub ahead of print]