If hormone treatment stops working for prostate cancer, doctors may use alternative treatments such as chemotherapy, radiotherapy, and immunotherapy.

Most prostate cancers eventually become resistant to hormone therapy. Doctors may then use alternative treatments depending on the individual case.

This article looks at why hormone therapy may stop working, and the types of treatments doctors may use for hormone-resistant prostate cancer.

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In the early stages, prostate cancer requires androgens, or male sex hormones, to grow. Hormone therapy helps to reduce or block androgens, which can then prevent prostate cancer from developing further.

Castration-resistant prostate cancer (CRPC) is a type of prostate cancer that is resistant to the following hormone treatments, called androgen deprivation therapy (ADT):

  • orchiectomy, which is the removal of one or both testicles
  • LHRH agonists or antagonists

CRPC may still respond to other types of hormone therapy.

Doctors may further categorize CRPC into:

  • nonmetastatic CRPC, meaning the cancer has not spread to other areas of the body
  • metastatic CRPC, meaning the cancer has spread to other areas, such as lymph nodes or bones

Why does hormone therapy stop working?

Over time, hormone therapy stops working for most cases of prostate cancer.

With CRPC, prostate cancer continues to grow despite very low or undetectable androgen levels.

Hormone therapy may stop working if cancer cells develop a resistance to the treatment. ADT may destroy some cancer cells, while others may adapt and evolve to become resistant to those hormone therapies.

Experts are not entirely sure why prostate cancer cells eventually become resistant to hormone therapy.

How do doctors tell if hormone therapy stops working?

To monitor how hormone therapy is working, a doctor will measure prostate-specific antigen (PSA) levels in the blood, as well as testosterone levels.

Rising PSA levels and low testosterone levels can indicate CRPC. Doctors may also use imaging tests to determine whether the cancer is growing.

If first-line hormone therapies have stopped working, doctors may use the following treatment options:

  • Complete androgen blockade: Androgen receptor blockers, such as enzalutamide, flutamide, or bicalutamide.
  • Abiraterone: A type of anti-androgen medication.
  • Immunotherapy: This uses sipuleucel-T, a vaccine that helps the immune system fight prostate cancer.
  • Chemotherapy: Doctors usually use the drug docetaxel for CRPC or cabazitaxel.
  • Targeted therapy: Rucaparib camsylate and olaparib are two types of targeted therapy drugs that may help treat CRPC that has mutations.
  • Radium-223 dichloride: Radium-223 dichloride is a type of radiotherapy drug that works inside the body to kill cancer cells with radiation.
  • Radiation therapy: Doctors may combine external radiation therapy with hormone therapy to destroy cancer cells and relieve pain or urinary problems.
  • Clinical trials: Clinical trials may offer new treatment options for people with prostate cancer that is resistant to standard treatments.

Doctors will continue to prescribe ADT as part of the treatment. This keeps testosterone levels low, as an increase in testosterone could contribute to tumor growth.

According to a 2021 review, in recent years, there have been improvements in treatment for CRPC, particularly metastatic CRPC, with many promising new treatments.

Clinical trials are currently underway to investigate new therapies for hormone-resistant prostate cancer.

Research in 2022 suggests that a combination of ADT with salvage prostate bed radiotherapy and pelvic lymph node radiotherapy may help to reduce prostate cancer progression.

A 2022 phase II clinical trial looked at the effects of carotuximab, a CD105 inhibitor, in combination with enzalutamide or abiraterone. This may be a beneficial treatment approach for prostate cancer that is resistant to androgen-blocking therapy.

Intermittent ADT

According to the National Cancer Institute (NCI), experts are investigating a technique called intermittent ADT that may delay the development of hormone resistance.

This technique involves the patient having breaks from hormone treatment rather than taking the medication continuously. The idea is that the cancer cells will take longer to build up resistance to the therapy.

So far, randomized trials have shown that people undergoing intermittent ADT have a similar outlook to those on continuous ADT. However, intermittent ADT seems to reduce some side effects.

Other treatments are available even when prostate cancer becomes resistant to hormone therapy.

According to the NCI, research has shown that treatment with abiraterone or enzalutamide in combination with ADT, compared to ADT alone, has improved survival rates in people with metastatic CRPC.

However, the outcome for CRPC may be poor. A 2021 Swedish study looked at 4,098 patients with CRPC. The mortality rate in this group was 57% for the lowest risk category and 89% for the highest.

The median overall survival time in this group was 1.86 years. The researchers also stated that, for a person with CRPC, this will likely become fatal.

To discover more evidence-based information and resources for prostate cancer, visit our dedicated hub.

This section answers some frequently asked questions about hormone treatments for prostate cancer.

How many times can you have hormone treatment for prostate cancer?

ADT is usually the first type of hormone therapy people will receive for prostate cancer.

If ADT stops working, people may receive further hormone therapy with different types of treatment, such as androgen receptor blockers or androgen synthesis inhibitors.

People may have hormone therapy in combination with other treatments, such as chemotherapy. Doctors will monitor how they respond to treatment and decide whether to continue hormone therapy or try a different treatment.

How long is hormone therapy for prostate cancer effective?

Doctors are unable to predict how long hormone therapy will be able to effectively prevent prostate cancer from growing.

Doctors will regularly test PSA levels in people taking hormone therapy longer than a few months. If PSA levels rise despite low androgen levels, it may be a sign that the current hormone therapy is no longer an effective treatment.

What is the newest treatment for prostate cancer?

In August 2022, the Food and Drug Administration (FDA) approved the drug darolutamide in combination with docetaxel to treat metastatic hormone-sensitive prostate cancer.

If first-line hormone therapy stops working, doctors may switch to different types of hormone treatments or other therapies, such as chemotherapy, immunotherapy, or radiotherapy.

A combination of treatment approaches may be the most beneficial for prostate cancer.