What Happens When Abiraterone Stops Working? A Comprehensive Guide
For patients with advanced prostate cancer, abiraterone acetate (marketed as Zytiga or its generic equivalents) is often a cornerstone of treatment. This groundbreaking medication has significantly improved survival rates and quality of life for men battling metastatic castration-resistant prostate cancer (mCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC). However, like many cancer therapies, abiraterone doesn’t work forever.
As prostate cancer becomes resistant to abiraterone, patients and their caregivers are left with an important question: What happens when abiraterone stops working? In this comprehensive guide, we’ll explore why abiraterone might lose its effectiveness, what signs to look for, and the next steps in treatment when this critical medication is no longer effective.
What Is Abiraterone and How Does It Work?
Before diving into what happens when abiraterone stops working, it’s important to understand how this medication functions and its role in prostate cancer treatment.
The Role of Androgens in Prostate Cancer
Prostate cancer cells rely on androgens (male hormones like testosterone) to grow and spread. Traditional hormone therapies, known as androgen deprivation therapy (ADT), reduce testosterone production in the testes. However, advanced prostate cancer can still grow by producing androgens in other parts of the body, such as the adrenal glands and tumor cells themselves.

How Abiraterone Works
Abiraterone is a next-generation hormone therapy that targets androgen production at its source. It works by inhibiting the enzyme CYP17A1, which is involved in the synthesis of androgens. This effectively starves cancer cells of the hormones they need to grow, slowing the progression of the disease.
Why Does Abiraterone Stop Working?
Rising PSA levels, worsening symptoms (e.g., bone pain or fatigue), or imaging scans showing disease progression are signs that abiraterone may no longer be effective. When abiraterone stops working, it means the cancer has become resistant, leading to disease progression. At this stage, alternative treatments like enzalutamide, chemotherapy, or clinical trials are explored to manage the condition.
Unfortunately, abiraterone is not a cure for prostate cancer. Over time, the cancer can develop resistance to the medication, meaning it will continue to grow and spread despite treatment.
1. Cancer Cell Adaptation
Cancer cells are incredibly adaptive. When abiraterone blocks androgen production, some cancer cells may evolve to survive without relying on androgens. This is referred to as androgen-independent or castration-resistant prostate cancer (CRPC).
2. Intratumoral Androgen Production
Even with abiraterone therapy, cancer cells may find alternative pathways to produce androgens within the tumor itself. These pathways can bypass the CYP17A1 enzyme, rendering abiraterone less effective.
3. Other Molecular Changes
Genetic mutations and changes in tumor biology can also contribute to resistance. For example:
- Mutations in the androgen receptor (AR) can make cancer cells more sensitive to very low levels of androgens.
- Activation of non-androgen pathways may allow cancer cells to continue growing despite androgen suppression.
4. Duration of Treatment
The longer a patient is on abiraterone, the higher the likelihood of resistance developing. Studies show that most patients eventually experience disease progression after 1–3 years of abiraterone therapy.

Signs That Abiraterone Is No Longer Working
It’s important for patients and caregivers to recognize the signs that abiraterone may have stopped working. Regular monitoring by a healthcare team is crucial to identify disease progression.
1. Rising PSA Levels
- The prostate-specific antigen (PSA) is a key biomarker for prostate cancer.
- A consistent rise in PSA levels during abiraterone treatment is often the first sign that the medication is losing its effectiveness.
2. Progressive Symptoms
- Patients may experience new or worsening symptoms, such as:
- Increased bone pain (indicating cancer spread to the bones).
- Urinary difficulties.
- Fatigue or weakness.
3. Radiographic Progression
- Imaging tests such as CT scans or bone scans may show that the cancer is growing or spreading to new areas.
4. Biochemical Progression
- Rising levels of other cancer markers (e.g., alkaline phosphatase or lactate dehydrogenase) can indicate disease progression.
What Happens When Abiraterone Stops Working?
When abiraterone is no longer effective, it means that the cancer has progressed despite treatment. This is a challenging moment for patients, but it’s important to remember that other treatment options are available. Here’s what typically happens next:
1. Reassessment of Disease
Your oncologist will perform a thorough evaluation to confirm disease progression. This may include:
- PSA testing.
- Imaging studies (e.g., MRI, CT scans, bone scans).
- Biopsies or genetic testing to better understand the cancer’s biology.
2. Exploration of Alternative Treatments
Once abiraterone stops working, your doctor will likely recommend a new treatment plan. The options depend on factors such as the extent of disease progression, previous treatments, and overall health.
Next Steps in Treatment: Options After Abiraterone
When abiraterone stops working, several treatment options are available:
1. Enzalutamide (Xtandi)
Enzalutamide is another next-generation androgen receptor inhibitor. Unlike abiraterone, it works by blocking the androgen receptor directly, preventing cancer cells from using androgens. It is commonly used after abiraterone in patients with advanced prostate cancer.
- How It Works: Prevents cancer cells from “reading” androgen signals.
- Efficacy: Studies show that enzalutamide can improve overall survival and delay disease progression in castration-resistant prostate cancer.

2. Chemotherapy
Chemotherapy is often the next step for patients with metastatic castration-resistant prostate cancer (mCRPC) after abiraterone fails.
- Common Drugs:
- Docetaxel: The most widely used chemotherapy for advanced prostate cancer.
- Cabazitaxel: An option for patients who have already received docetaxel.
- How It Works: Kills rapidly dividing cancer cells throughout the body.
While chemotherapy can have side effects, it remains an important option for controlling advanced disease.
3. Radiopharmaceuticals
For patients with bone metastases, radiopharmaceuticals like Radium-223 (Xofigo) can help relieve pain and reduce complications.
- How It Works: Delivers targeted radiation to bone tumors, killing cancer cells and slowing disease progression.
4. PARP Inhibitors
PARP inhibitors like olaparib (Lynparza) are a newer class of drugs that target specific genetic mutations, such as BRCA1/2 mutations, in prostate cancer.
- Eligibility: Patients with genetic testing that reveals mutations in DNA repair genes.
- Efficacy: Shown to improve progression-free survival in certain patients.
5. Immunotherapy
While immunotherapy has shown limited effectiveness in prostate cancer, certain options may be considered, such as:
- Sipuleucel-T (Provenge): A personalized cancer vaccine for metastatic prostate cancer.
6. Clinical Trials
Participating in a clinical trial can provide access to cutting-edge treatments that are not yet widely available. Discuss this option with your doctor if other treatments have been exhausted.
Coping When Abiraterone Stops Working
Hearing that your current treatment is no longer effective can be distressing, but it’s important to stay proactive and focused on your options. Here are some tips for coping:
1. Stay Informed
Learn about your disease and the available treatment options. Being well-informed can help you make confident decisions about your care.
2. Lean on Your Support System
Rely on family, friends, and support groups to help you through this challenging time. Talking to others who have experienced similar situations can be especially comforting.
3. Communicate with Your Healthcare Team
Maintain open and honest communication with your oncologist and care team. Don’t hesitate to ask questions or seek second opinions if needed.
4. Consider Palliative Care
Palliative care can help manage symptoms, improve quality of life, and provide emotional support during treatment transitions.

The Future of Prostate Cancer Treatment
Research into prostate cancer is advancing rapidly, and new treatments are being developed to overcome resistance to medications like abiraterone. Promising areas of research include:
- Next-Generation Hormone Therapies: Drugs that target alternative androgen pathways.
- Targeted Therapies: Treatments tailored to specific genetic mutations or biomarkers.
- Combination Therapies: Combining drugs like abiraterone with other agents to improve outcomes.
With these advancements, patients can look forward to more options and better outcomes in the future.
Conclusion: What Happens When Abiraterone Stops Working?
When abiraterone stops working, it marks a transition point in prostate cancer treatment. While this can be a difficult and emotional time, it’s important to remember that there are still many options available. From alternative hormone therapies to chemotherapy, immunotherapy, and clinical trials, your healthcare team will work with you to create a new treatment plan tailored to your needs.
The journey with advanced prostate cancer can be challenging, but with the right resources, support, and medical care, patients can continue to fight the disease and maintain their quality of life. If you’re in this situation, don’t hesitate to reach out to your doctor, support groups, or financial assistance programs to help you through the next phase of treatment.
1. How do you know if abiraterone has stopped working?
Rising PSA levels, worsening symptoms (e.g., bone pain or fatigue), or imaging scans showing disease progression are signs that abiraterone may no longer be effective.
2. What are the next treatment options after abiraterone stops working?
Options include enzalutamide, chemotherapy (e.g., docetaxel), radiopharmaceuticals (e.g., Radium-223), PARP inhibitors, immunotherapy, or clinical trials.
3. Can abiraterone be restarted later if it stops working?
Abiraterone is unlikely to be effective again after resistance develops. Doctors usually recommend switching to a different therapy tailored to the cancer’s progression.