AUA Guidelines for Metastatic Castration-Resistant Prostate Cancer

The American Urological Association recently released its first set of treatment guidelines addressing the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) at its 2013 Annual Meeting.

The guidelines were released to address the increasingly complex treatment landscape available for patients with mCRPC. According to the guideline, prior to 2004, patients with mCRPC who failed primary androgen therapy were treated only for palliation.

“In the last few years, there have been many new FDA approved agents for men with mCRPC,” said Michael S. Cookson, MD, vice chair of the department of urologic surgery at Vanderbilt University Medical Center.

In 2004, docetaxel was approved to treat mCRPC. More recently, the newly approved drugs include sipuleucel-T (Provenge), cabazitaxel (Jevtana), abiraterone acetate (Zytiga), and enzalutamide (Xtandi).

“Because of the emergence of these new treatments, which have improved survival in these men, it is difficult for clinicians to understand how and when to use these new agents, and where their effectiveness may be,” Dr. Cookson, who chaired the panel that developed the guideline, told Cancer Network.

Last week, the FDA also granted approval to radium 223 dichloride (Xofigo) for mCRPC that has metastasized to the bone.

Dr. Cookson acknowledged that the members of the guideline panel new that this approval may be coming; however, the guideline “had to stop somewhere,” he said. The data supporting the approval of radium 223 has not yet been published, and, therefore, could not be put through the rigorous literature review required for evidence included in the AUA guideline.

“The limitation of the guidelines is that they are going to need to be updated,” Dr. Cookson said. “This is a rapidly evolving field.”

The guidelines included six difference index patients created based on the presence or absence of metastases, performance status, degree of symptoms, and prior treatment with docetaxel.

Index patient 1 was described as having asymptomatic, non-metastatic CRPC.

• Clinicians should offer: Observation with continued androgen-deprivation therapy recommended.

• Clinicians may offer: Treatment with first-generation anti-androgen therapy (flutamide, bicalutamide, and nilutamide), or ketoconazole plus steroid if patient declines observation only.

• Clinicians should not offer: Systemic chemotherapy or immunotherapy outside of clinical trial.

Index patient 2 had asymptomatic or minimally symptomatic mCRPC without prior docetaxel.

• Clinicians should offer: Abiraterone plus prednisone, docetaxel, or sipuleucel-T to patients with good performance status.

• Clinicians may offer: First-generation anti-androgen therapy, ketoconazole plus steroid, or observation to patients with good performance status who do not want or cannot have one of the standard therapies.

Index patient 3 has symptomatic mCRPC with good performance status and no prior chemotherapy.

• Clinicians should offer: Docetaxel.

• Clinicians may offer: Abiraterone plus prednisone, or ketoconazole plus steroid, mitoxantrane, or radionuclide therapy to patients who do not want or cannot have one of the standard therapies.

• Clinicians should not offer: Estramustine or sipuleucel-T.

Index patient 4 has symptomatic mCRPC with poor performance status and no prior docetaxel chemotherapy.

• Clinicians may offer: Abiraterone plus prednisone, ketoconazole plus steroid, or radionuclide therapy to patients who are unable or unwilling to receive abiraterone plus prednisone. Docetaxel or mitoxantrone can be offered in select cases, specifically when performance status is related to cancer.

• Clinicians should not offer: Sipuleucel-T.

Index patient 5 has symptomatic mCRPC with good performance status and prior docetaxel.

• Clinicians should offer: Abiraterone plus prednisone, cabazitaxel, or enzalutamide. If abiraterone plus prednisone was given prior to docetaxel, offer cabazitaxel or enzalutamide.

• Clinicians may offer: ketoconazole plus steroid, if abiraterone plus prednisone, cabazitaxel, or enzalutamide is unavailable. Docetaxel may be offered to patients who are benefitting at the time of discontinuation due to reversible side effects.

Index patient 6 has symptomatic mCRPC with poor performance status and prior docetaxel therapy.

• Clinicians should offer: Palliative care. For select patients, abiraterone plus prednisone, enzalutamide, ketoconazole plus steroid, or radionuclide.

• Clinicians should not offer: Systemic chemotherapy or immunotherapy.

The guideline also makes key statements regarding bone health in patients with mCRPC:

• Clinicians should offer preventative treatment for fractures and skeletal-related events to CRPC patients.

• Clinicians may choose either denosumab or zoledronic acid when selecting a preventative treatment for skeletal-related events for mCRPC patients with bony metastases.