Treatments for Castration Resistant Prostate Cancer

Once advanced prostate cancer develops resistance to hormone therapy, otherwise known as castration resistant prostate cancer, it becomes a real challenge to treat. Resistance is usually discovered once your prostate-specific antigen (PSA) level continues to rise without signs of abating despite continued hormone therapy.

While the commonly used androgen deprivation therapy may work for a long time in many men to reduce testosterone levels and control the cancer, eventually, castration resistance does develop. Initially, this therapy places increasing pressure on the cancer to stop growing. However, the disease then evolves to rely on alternative strategies to grow. This allows the cancer to keep progressing, even once testosterone levels have been reduced to castrate levels.

When it comes to treating local castration resistant prostate cancer, the greatest concern is whether your cancer would spread soon. If your PSA level doubles in less than ten months, you would be at higher risk of cancer metastasis. Recommended treatment includes continuing androgen deprivation therapy while taking an additional androgen pathway blocker such as apalutamide, darolutamide, or enzalutamide. However, if your PSA does not rise quickly, your doctor may recommend observation first, before considering changes to your treatment plan. Systemic chemotherapy or immunotherapy may not be recommended at this stage, unless it is under a clinical trial.

Before the approval of the chemotherapy docetaxel in 2004, the main approach to managing metastatic castration resistant prostate cancer was palliative and focused on improving one’s quality of life rather than seeking a cure. However, with the introduction of docetaxel, treatment for advanced prostate cancer improved immensely. Current recommendations include continued androgen deprivation therapy, together with either abiraterone, docetaxel, or enzalutamide.

Generally, while multiple combinations of drugs may be used in treating advanced prostate cancer, your doctor will likely recommend treatments with an alternative mechanism of action for a greater chance of seeing new success. Other treatments available include:

• Cabazitaxel

If the first-line docetaxel chemotherapy no longer works for you, a newer alternative chemotherapy would be cabazitaxel, which is also derived from the same family.

• Sipuleucel-T

The personalized vaccine sipuleucel-T trains your own immune cells to attack prostate cancer cells and may be recommended for those with minimal symptoms.

• Radium-223

If your cancer has spread to the bones and you are symptomatic, radiation therapy wielding radium-223 may be considered, as long as you are free from issues with other major organs or heavy swelling of the lymph nodes.

• Olaparib/Rucaparib

If you are found to have a specific mutation in the BRCA gene, you may be recommended the newly approved olaparib or rucaparib as an alternative treatment after other options have been exhausted. Both work by inhibiting the genetic repair in the cancer cells, preventing them from repairing any damage, making it harder to persist.

• Pembrolizumab

If you have mutations that lead to dysfunctional DNA repair systems or high instability in your tumor’s genes, you may be offered pembrolizumab once other options have been exhausted. This is another therapy that targets your immune system, helping it to better recognize and attack cancer cells.

• ¹⁷⁷Lu-PSMA-617

¹⁷⁷Lu-PSMA-617 is another new radiation therapy that helps treat advanced prostate cancer, by binding to specific targets on cancer cells. It can be considered after trying androgen deprivation therapy and chemotherapy. However, you will need to undergo a scan to check if you have enough suitable targets for successful treatment.

Additionally, if you are continuing androgen deprivation therapy after progression to advanced prostate cancer, you may be recommended preventative treatment to protect your bones from damage or fractures. This can include taking calcium or vitamin D supplements, stopping smoking or exercises that rely on your body weight. Alternatively, if you are at high risk of fractures, you may be given bisphosphonates or denosumab, inhibitors of bone breakdown.

At this stage, prostatectomy, the surgical removal of the prostate, is generally no longer considered, and instead remains reserved for local prostate cancer that has not yet spread. Its goal is to remove all cancerous tissue, which is difficult once the cancer has already spread beyond the prostate.

In the past, chemotherapy alone used to be the best treatment for this advanced prostate cancer. However, progress over the years has brought along many new ways to treat castration resistant prostate cancer. You and your doctor would be in the best position to discuss the right choice for you, especially based on your past treatment history.

If you are keen, you can also consider clinical trials that your doctor recommends you to access newer experimental treatments. While this is a challenging place to be, many new treatment combinations do hold hope for progress in the field.