Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer Patient Summary

Publication Date: April 4, 2023

Last Updated: May 19, 2023

Overview

This patient guideline summarizes key takeaways from American Society of Clinical Oncology (ASCO) guidelines for the Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer. The purpose of this guideline is to provide new evidence-based recommendations on critical issues affecting the care of men with noncastrate advanced, recurrent, or metastatic prostate cancer.

This patient summary focuses on prostate cancer that is one or more of the following:
- “recurrent” - which means that cancer has returned after prior treatment. It may come back to the prostate area again, or in other parts of the body.
- “advanced” - which means the cancer is stage IV (pronounced :four") and less likely to be controlled.
- “metastatic” - which means the cancer has spread to other parts of the body.
- “de novo metastatic ” - which means that the cancer is already metastatic by the time you are diagnosed.
- “noncastrate prostate cancer (NCPC)” - which means the cancer is responsive to androgen treatments that lower hormones..

Risk and Volume

The management of noncastrate advanced, recurrent, or metastatic prostate cancer depends on many factors, including the disease activity when you are diagnosed, your prior treatments, your “risk” level, the “volume” level, and your personal preferences.

One of the most important factors that guide treatment decisions is determining whether you have a low-volume disease or a high-volume disease.
- High volume disease (HVD) is defined as four or more bone metastases, one or more of which is outside of the spine or pelvis, and/or the presence of any visceral disease. Note: visceral organs are those located within the body's main cavities, such as the brain, lungs, liver, or intestines. Visceral disease refers to the presence of cancerous metastases in these organs.
- Low-volume disease (LVD) is anything that is not classified as high volume.

Another important factor is determining whether the cancer is defined as high risk or low risk.
- High risk is defined as having at least two of the following factors:
  - Gleason Score greater than or equal to 8, which means the cells look very different from healthy cells, they are "poorly differentiated" or "undifferentiated"
  - 3 or more lesions on bone scan
  - Visceral metastases, excluding lymph node metastases.
- Low risk is defined as anything that is not classified as high risk

Treatment Overview

One of the most common treatments for noncastrate advanced, recurrent, or metastatic prostate cancer is called androgen deprivation therapy (ADT).

Androgens are male hormones, and lowering androgen levels or stopping them from getting into prostate cancer cells often makes prostate cancers shrink or grow more slowly for a time. However, ADT alone does not cure prostate cancer. It is most effective when paired with additional therapies.

The standard of care (SOC) for noncastrate advanced, recurrent, or metastatic prostate cancer includes a mixture of ADT and one of the following five types of medications.
- Darolutamide (NUBEQA)
- Abiraterone (ZYTIGA)
- Enzalutamide (XTANDI)
- Apalutamide (ERLEADA)
- Docetaxel (TAXOTERE)

Three or more of these medications may also be combined in what is called “triplet therapy”.

The best medications to use vary for each patient based on multiple factors, including disease stage, activity and patient preference.

Specific Treatments

ADT, Docetaxel and Darolutamide

If you have metastatic NCPC and high-volume disease (HVD), and are a candidate for treatment with chemotherapy, but are unwilling or unable to receive triplet therapy, docetaxel plus ADT is a recommended therapy option. (, , , )

The most common reason a patient is unable or unwilling to receive triplet therapy is due to high cost and a lack of insurance coverage for the therapy.
Docetaxel plus ADT has inferior overall survival rates compared to triplet therapy.

615

If you have de novo (newly diagnosed) metastatic NCPC and HVD, and are being offered ADT plus docetaxel chemotherapy, triplet therapy (abiraterone and prednisone plus ADT and docetaxel) is a recommended therapy option. (, , , )

615

If you have low-volume metastatic disease and are a candidate for chemotherapy, the combination of docetaxel plus ADT should not be used, since it is not a recommended therapy option. (, , , )

615

If you have de novo metastatic NCPC and are being offered ADT plus docetaxel chemotherapy, triplet therapy (darolutamide plus ADT and docetaxel) is a recommended therapy option. (, , , )

615

If you have metastatic NCPC treated with darolutamide, docetaxel, and ADT, the recommended regimen is:

Darolutamide - 600 mg as two 300 mg tablets orally with food, twice daily (to a total daily dose of 1200 mg)
Docetaxel - 75 mg/m2, and should begin within 6 weeks of the first dose of darolutamide. Docetaxel should be administered through an IV once every 3 weeks for up to six cycles.
If cost is a concern, talk to your care provider about the cost of darolutamide treatment compared with other options, such as abiraterone.

(, , , )

615

If you have metastatic NCPC and are being treated with docetaxel, the recommended regimen is: six doses administered once at 3-week intervals at 75 mg/m2 either alone or with prednisolone. (, , , )

If you have not been diagnosed with de novo metastatic disease or HVD, you should not be taking docetaxel, since it is not a recommended therapy option.

615

ADT Plus Abiraterone

If you have high-risk de novo metastatic NCPC, the addition of abiraterone to ADT is a recommended therapy option. (, , , )

615

If you have low-risk de novo metastatic NCPC, ADT plus abiraterone is a recommended therapy option. (, , , )

615

If you have metastatic NCPC and you are taking abiraterone, the recommended regimen is 1,000 mg with either prednisolone or prednisone 5 mg once daily until progressive disease is documented, meaning the treatment is no longer working. (, , , )

615

ADT Plus Enzalutamide

If you have metastatic NCPC, ADT plus enzalutamide is a recommended therapy option. (, , , )

This recommendation applies both to patients with newly diagnosed metastatic disease and also to those who have received prior therapies, such as radical prostatectomy or radiotherapy for localized disease.

615

If you have metastatic NCPC and you are taking enzalutamide, the recommended regimen is 160 mg once per day with ADT. (, , , )

If cost is a concern, talk to your care provider about the cost of darolutamide treatment compared with other options, such as abiraterone.

615

Combination Therapies for Noncastrate Locally Advanced Non-Metastatic Disease

If you have locally advanced, non-metastatic prostate cancer, ADT plus abiraterone and prednisolone is a recommended therapy option. (, , , )

ADT plus abiraterone is recommended over castration monotherapy.

615

If you have locally advanced, non-metastatic prostate cancer and drugs such as abiraterone may not be available, combined androgen blockade using ADT plus a first-generation antiandrogen, is a recommended therapy option. (, , , )

Examples of first-generation antiandrogens include: flutamide, nilutamide, and bicalutamide. Combined androgen blockade using ADT plus a first-generation antiandrogen is recommended over castration monotherapy.

615

Early Androgen Deprivation for Noncastrate Locally Advanced Non-Metastatic Disease

If you initially present with noncastrate locally advanced non-metastatic disease, and have not undergone previous local treatment and are unwilling or unable to undergo radiation therapy (RT), early (immediate) ADT may be a treatment option to consider. (, , , )

Talk to your care provider about early ADT to learn more about the risk of short- and long-term side effects.
Deferred ADT is preferred by patients who desire to avoid, or at least delay, potential ADT side effects.
If you are symptomatic (which means you are experiencing symptoms), deferred ADT may not be right for you.

615

Intermittent Androgen Deprivation for Recurrent Nonmetastatic Disease

Intermittent androgen deprivation therapy (IADT) involves periods of treatment lasting several months that alternate ADT with “drug holidays," (off-treatment periods). The goal of IADT is to reduce side effects and improve overall quality of life, while still providing the clinical benefits of ADT. (, , , )

615

If you have high-risk biochemically recurrent non-metastatic prostate cancer after previous treatment with radical prostatectomy (RP) and/or radiation therapy (RT), intermittent androgen deprivation therapy may be a treatment option to consider. (, , , )

Biochemically recurrent prostate cancer means that a blood test has shown that your PSA levels are rising.
If you are considering IADT, you should be made aware of the potential benefits of IADT associated with the off-treatment intervals. These include reduced treatment side effects, quality-of-life benefits, and lower cost.
Patients taking IADT require close follow-up, so you must attend frequent doctor visits for monitoring, even during off-treatment periods.

615

Figure 1. Initial Management of Noncastrate Metastatic Prostate Cancer (Updated)

Shared Decision-Making and Patient-Clinician Communication

It is important to understand that prostate cancer medications may have side effects. Common side effects associated with ADT are depression, dementia (brain disorder that impairs memory, thinking, and behavior), stroke, heart problems, deep venous thrombosis (blood clot in the veins), hot flushes, fatigue, and nausea.

Shared decision-making between you and your care provider is very important. The more knowledgeable you can become about your treatment choices, and the potential risks and benefits, the more likely it is that you and your care provider will make the best possible choice for your situation.

When choosing a treatment choice, consider the following:
- Current insurance coverage
- Cost of treatment and availability of lower-cost alternatives
- Survival benefits vs. side effects and quality of life
- The stage and progression of your prostate cancer when starting initial ADT
- Logistics for getting to and from treatments and other care visits
- Friends, family, and your current support network
- And more

Ask your care provider about additional resources, including support from social workers, to help you make the best possible decisions for your treatment.

Regardless of treatment choice(s), you should consider putting a survivorship plan and road map in place to reduce the uncertainty about what lies ahead during your treatment.

Unfortunately, disparities do exist in health care. Patients with cancer who are members of racial or ethnic minorities are more likely to suffer from comorbidities, experience more substantial obstacles to receiving care, are more likely to be uninsured, and are at greater risk of receiving poorer quality care than other Americans. Many patients may also lack access to care because of their geographic location and distance from appropriate treatment facilities. Awareness of these disparities in access to care should be taken into account. Talk to your care provider if you believe you may face difficulties during treatment as a result of these disparities.

Additional Resources

Abbreviations

ADT: Androgen Deprivation Therapy
HVD: High-volume Disease
IADT: Intermittent Androgen Deprivation Therapy
LVD: Low-volume Disease
NCPC: Noncastrate Prostate Cancer
PSA: Prostate-specific Antigen
RP: Radical Prostatectomy
RT: Radiation Therapy

Source Citation

Virgo KS, et al. Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Focused Update. J Clin Oncol. 2023 April 3. doi: 10.1200/JCO.23.00155.

Virgo KS, et al. Initial Management of Non-Castrate Advanced, Recurrent or Metastatic Prostate Cancer: ASCO Guideline Update. J Clin Oncol. 2021 January 26. doi: 10.1200/JCO.23.03256.

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.