Androgen Deprivation Therapy: The Foundation Of Advanced Prostate Cancer Treatment

By reducing or blocking testosterone, ADT can slow down the growth of cancer or even shrink it. ADT does not cure prostate cancer, but it is very effective at controlling it, especially when the disease is more aggressive or has spread beyond the prostate. In some cases, additional treatments are added to control the disease.

“We know that androgen deprivation therapy (ADT) alone, or lowering a man’s hormone levels through either shots or pills, are usually not enough to give them a long-term remission,” Dr. Leonard Gomella, Chair of Urology at Thomas Jefferson University’s Sidney Kimmel Comprehensive Cancer Center in Philadelphia, explains.

“We’ll usually add something else, such as a pill on top of the androgen deprivation therapy (ADT) to further weaken the cancer and improve a man’s outcome,” he adds.

How Does ADT Work?

There are a few ways doctors can reduce the effects of testosterone in the body, including medications and surgery.

Most men receive ADT through injections or pills that either stop testosterone from being made or block it from reaching the cancer cells.

There are two main types of medications:

• LHRH analogues (agonists or antagonists): These drugs tell the body to stop producing testosterone. Common injections include leuprolide (Lupron or Eligard [agonists]) and degarelix (Firmagon [antagonist]).
• Anti-androgens: These pills (like bicalutamide or enzalutamide) block testosterone from attaching to cancer cells. Sometimes, these are used together with LHRH analogues for a stronger effect.

Another way to lower testosterone is through the surgical removal of the testicles (orchiectomy). This is a one-time procedure that works quickly and permanently. While very effective, many men prefer medication over surgery for emotional or personal reasons.

When Is ADT Used?

ADT is not needed for every man with prostate cancer, but it plays a key role in several situations, including the following:

1. Intermediate or high-risk localized prostate cancer: When prostate cancer is still within the prostate but has features that make it more likely to grow or spread (e.g. a PSA ≥ 10 ng/mL, Gleason score ≥ 7, or fast growth), a finite duration of ADT is often used alongside radiation therapy. This combination helps improve outcomes and reduce the risk of the cancer coming back.
2. Locally advanced prostate cancer: If the cancer has grown outside the prostate but has not spread far, a finite duration of ADT is often used with radiation to control the disease.
3. Metastatic prostate cancer: When prostate cancer has spread to other parts of the body (like bones or lymph nodes), ADT becomes the backbone of systemic treatment. It helps control symptoms, improves quality of life, and prolongs survival.
4. Rising PSA after surgery or radiation: If a man’s PSA begins to rise after initial treatment (called biochemical recurrence [BCR]), ADT may be used to slow down the return of prostate cancer.

What Are The Side Effects Of ADT?

Because testosterone affects many parts of the body, reducing its levels can lead to side effects. These can vary from person to person, and some may be more bothersome than others.

Common side effects include:

• Hot flashes
• Loss of sexual desire and erectile dysfunction
• Fatigue
• Cognitive dysfunction
• Depression or mood swings
• Weight gain (metabolic syndrome)
• Muscle loss
• Mood changes
• Bone thinning (osteoporosis)
• Breast pain or enlargement (gynecomastia)
• Cardiovascular complications
• Increased risk of other health problems

There are many methods that can be used to help manage these side effects. Regular exercise (especially strength training) can help with fatigue and muscle loss. Calcium and vitamin D supplements, along with bone density tests, can help protect your bones.

Patients should also speak to their doctors about sexual health, mental health, and ways to reduce heart risks associated with treatment.

What If ADT Doesn’t Work?

In many men, ADT works well for years. But over time, prostate cancer cells can adapt and start growing again — even when testosterone levels are very low. This is called castration-resistant prostate cancer (CRPC).

Some of the treatments available for CRPC include:

1. Androgen receptor pathway inhibitor (ARPI) or hormone therapy: Hormonal drugs like abiraterone or enzalutamide starve the cancer by blocking the cancer’s ability to use even tiny amounts of androgens.
2. Chemotherapy: Drugs like docetaxel or cabazitaxel kill the cancer cells even when hormone treatments are no longer enough.
3. Radioligand therapy (RLT): Radioligand drugs that use radioactive isotopes with ligands to target prostate cancer cells and kill them. Radium-223 is an alpha-emitting radiotherapeutic drug that mimics calcium (calcimimetic) that targets bone metastases. Lutetium Lu 177 vipivotide tetraxetan is a beta-emitting radiotherapeutic drug that targets prostate cancer cells expressing prostate-specific membrane antigen (PSMA).
4. Immunotherapy: Drugs that help boost the patient’s immune system to attack cancer. Sipuleucel-T is a vaccine that can be used in asymptomatic or minimally symptomatic prostate cancer. Pembrolizumab can be used for prostate cancers that have a high tumor mutational burden (TMB) and/or mismatch repair deficiency (MMR deficiency or dMMR).
5. PARP inhibitor: A class of drugs (e.g. olaparib, rucaparib) that target specific genetic changes (e.g. BRCA1, BRCA2) in prostate cancer cells.

Even when ADT stops working on its own, it is usually continued alongside these newer treatments, as keeping testosterone low still provides clinical benefit to the patient.

Questions To Ask Your Doctor

• Will ADT be part of my treatment plan?
• What sort of side effects should I expect?
• What lifestyle changes can I make to help with side effects?
• What can we do if ADT does not work or stops working?

Content independently created by SurvivorNet with support from Novartis Pharmaceuticals Corp.

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