When My Cancer Becomes Resistant To Hormone Therapy: What Are Your Options?

“Once a patient is diagnosed with castrate-resistant prostate cancer, [the next step] really depends on what treatments they have already tried before they develop resistance,” Dr. Neha Maithel, a medical oncologist at Memorial Hermann Cancer Center in Houston, tells SurvivorNet. We now have novel hormone therapies that we can try in conjunction with the prior ADT to help prevent cancer from growing and get that PSA level back down.”

The first step is to check that your testosterone level is truly at castrate levels, review PSA trends, and repeat imaging as needed. Often, you’ll continue your original hormone therapy while adding another treatment, because different drugs block the cancer’s androgen-signaling in different ways. If PSA is rising very slowly and you feel well, some men can safely watch and wait with close monitoring before switching treatments.

What Are My Options?

Once your team has confirmed you have castration-resistant disease, they will need to learn if you have a controlled disease status, meaning no disease in other organs (metastases), or otherwise (no metastases). Aligned with other features, including overall health status, prior therapy, age, expectations, and comorbidities, this information will shape and guide further steps.

For men with a rising PSA but no metastases on imaging, newer androgen-receptor pathway inhibitors (ARPIs), such as apalutamide, enzalutamide, or darolutamide, are standard choices used alongside ongoing ADT. These medicines delay the spread and tend to be well-tolerated; your doctor will match the option to your health history and side-effect profile.

In some cases, there will be signals of disease in new regions, and the treatment becomes a sequence, chosen and adjusted over time. Many men start with (or switch to) a newer hormone-pathway drug called an ARPI (abiraterone, enzalutamide, apalutamide, or darolutamide). If symptoms are present or the cancer is moving quickly, chemotherapy, usually docetaxel, and later cabazitaxel if needed, can shrink tumors and reduce pain.

Your doctor may also talk about radioligand therapy that targets specific “gates” on the tumor cell surface, called PSMA (prostatic-specific membrane antigen).

PSMA is an antigen “found in 85% of prostate cancer cells,” Dr. Maithel says. “…We now have imaging that detects that PSMA and if your cancer is detected by that imaging, we can give those radioligands to attack the cancer directly.”

Lutetium Lu-177 vipivotide tetraxetan (Pluvicto) is FDA-approved for PSMA-positive metastatic castrate-resistant prostate cancer after an ARPI. An update in March 2025 stated it can be used earlier in eligible people to delay starting chemotherapy.

Making Treatment Choices

There isn’t one “right” treatment for everyone once ADT stops controlling the cancer.

Prostate Cancer UK and the American Cancer Society both emphasize that the best plan depends on where the disease is located, which treatments you’ve already received, your other health conditions, potential side effects, and, most importantly, your goals.

Some men want to delay chemotherapy; others prioritize the most aggressive option first. Both approaches can be reasonable. Bring a partner or friend to follow-up appointments, ask for a written summary, and give yourself permission to sleep on big decisions.

Questions To Ask Your Doctor

• My PSA is rising, but I feel well. Is that still a resistant disease?
• How long do I need to take the ADT to learn if my cancer is resistant or not?
• What should I take into account when weighing my treatment options now?
• Why is my cancer resistant to ADT? Does this mean it has a different prognosis?
• Are there any clinical trials that I could be a suitable candidate to enroll in?

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

 

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