Hormone Therapy for Advanced Prostate Cancer

Out of all cancers, prostate cancer has the best outlook at five years after diagnosis, with overall survival standing at 98%. However, once spread beyond the prostate, this drops to 31%.

The plan for advanced prostate cancer treatment should focus on life expectancy, your personal preferences and the characteristics of your tumor. Metastatic but castration sensitive prostate cancer is still able to respond to one of the first-line treatments for advanced prostate cancer, hormone therapy, otherwise known as androgen deprivation therapy. This is a surgical or drug-mediated reduction of male sex hormones, with the goal of slowing prostate cancer growth.

Androgen deprivation therapy includes the following options, which are generally considered equally effective.

Luteinizing hormone-releasing hormone (LHRH), also known as the gonadotropin-releasing hormone (GnRH), is a hormone that regulates the release of gonadotropins required to maintain reproductive health. LHRH agonists will bind to the LHRH cell receptors to promote their actions.

• Leuprolide
  Leuprolide is an injected treatment that binds to and overloads the receptors of your pituitary gland, alerting it to stop producing testosterone. However, this process may take a while, and instead exacerbate testosterone levels for a short period, causing a temporary “testosterone flare” of side effects, before testosterone levels are finally brought down.

LHRH antagonists are drugs that bind to the LHRH or GnRH cell receptors to inhibit their actions.

• Relugolix and degarelix
  Relugolix (also known as Orgovyx) and degarelix (also known as Firmagon) are treatments that bind to the receptors of the pituitary gland to inhibit the release of gonadotropins, in order to lower testosterone levels. Relugolix is taken orally, while degarelix is delivered by injection.

This surgery will remove both testes in order to stop their testosterone production. After this procedure, you may face greater difficulties with ejaculation. Notably, without the testes, you lose your ability to produce sperm. If you undertake this procedure, you may need to consider making preparations for sperm banking or other fertility interventions if you plan to have children in the future.

To avoid the development of resistance to androgen deprivation therapy, a more aggressive approach may add on the following treatments.

Androgen pathway blockers

• Abiraterone and prednisone
  Abiraterone (also known as Zytiga) is an androgen production inhibitor taken orally. It blocks an alternative source of androgen production, the adrenal glands. When used in combination with androgen deprivation therapy, it ensures that testosterone is reduced to undetectable levels. Prednisone, an anti-inflammatory steroid medication, is also taken with abiraterone to mitigate its side effects.
  
  
• Apalutamide, enzalutamide or darolutamide
  Apalutamide, enzalutamide and darolutamide (also known as Erleada, Xtandi and Nubeqa respectively) are androgen receptor inhibitors taken orally, which block androgens from binding to prostate cancer cells, with the goal of stopping cancer growth.

Chemotherapy

• Docetaxel
  Docetaxel (also known as Taxotere) is a chemotherapy given intravenously, and combined with prednisone to mitigate its side effects. It inhibits cancer cell growth by interrupting microtubule development, an essential structural component of cells.

While androgen deprivation therapy is now critical to treating advanced prostate cancer, it is commonly associated with side effects such as reduced sexual function (e.g. erectile dysfunction, low libido or shrinking of your penis or testes), weight gain, fatigue, hot flashes and loss of bone density or muscle mass. You should note however, that it does bring about difficult changes. Recovery from reduced sexual function is unlikely, with less than 20% of men continuing with sexual activity post-treatment.

The benefits of LHRH/GnRH antagonists and orchiectomy over LHRH/GnRH agonists are their quick results, and that they allow you to avoid the side effects of “testosterone flare” for the first few weeks.

However, orchiectomy is an irreversible process, which permanently impacts your fertility and how you look. While high-quality prosthetic solutions are available, it would be a personal choice whether you are comfortable proceeding with it.

Beyond that, your decision may rely on your preferences here:

• Are you comfortable with undergoing surgery?
• Would you prefer to finish your treatment in one session (e.g. surgery) or across multiple sessions (e.g. regularly taking medicine)?
• Are you comfortable with surgery being irreversible, as compared to drug therapy?

While the outlook for metastatic castration sensitive prostate cancer has improved over the past decade with many new agents being developed, it still remains a challenge to overcome the disease before progression to resistance against castration. As a result, strategies to deal with the disease remain aggressive. Talking to your doctor to understand your risk of side effects can help you to set realistic expectations for your life post-treatment.

Learn more: Treatments for Castration Resistant Prostate Cancer