Responding to the many new options available for the treatment of metastatic castration-resistant prostate cancer (mCRPC), the American Urological Association (AUA) has released new guidelines intended to help clinicians determine which agents to use and how to sequence them according to the patient’s clinical situation.
“Prostate cancer deaths are typically the result of mCRPC, a painful disease for which, until recently, the only treatments available were palliative,” said Michael Cookson, MD, from Vanderbilt-Ingram Cancer Center, Nashville, TN, who chaired the panel that developed the guidelines. “In recent years, a number of new treatments and therapeutic agents have entered the market that have been shown to minimize adverse effects and pain and prolong survival in some patients.”
Four distinct therapies have been approved for mCRPC in just the past 3 years: abiraterone (Zytiga®), an androgen biosynthesis inhibitor; cabazitaxel (Jevtana®), a microtubule inhibitor; enzalutamide (Xtandi®), an androgen receptor inhibitor; and sipuleucel-T (Provenge®), an autologous immunotherapeutic agent. Docetaxel, approved in 2004, was the first agent shown to improve survival in mCRPC.
To assist in clinical decision-making, the new AUA guidelines are structured around six index patients who represent the most common clinical scenarios encountered in clinical practice. The index patients were defined by the presence or absence of metastatic disease, the severity of symptoms, the patient’s performance status, and whether the patient has received prior treatment with docetaxel-based chemotherapy. The AUA urges practitioners to use the guidelines in conjunction with the current literature and the patient’s treatment goals (Table 1).1
Table 1. Most Common Prostate Cancer Scenarios Encountered in Clinical Practice and AUA Recommendations for Treatment1
|Index Patient Scenarios|| Recommendations
|Asymptomatic, non-metastatic CRPC||
• Observation with continued androgen deprivation
• Treatment with first-generation anti-androgens (flutamide,
bicalutamide, and nilutamide) or first-generation androgen
synthesis inhibitors (ketoconazole plus steroid) to patients
who are unwilling to accept observation.
• Do NOT offer systemic chemotherapy or immunotherapy outside the context of a clinical trial.
|Asymptomatic or minimally symptomatic, mCRPC without prior docetaxel chemotherapy||
• Offer abiraterone plus prednisone, docetaxel or sipuleucel-T
• Offer first-generation anti-androgen therapy, ketoconazole plus steroid or observation to these patients who do not want or cannot have one of the standard therapies.
|Symptomatic, mCRPC with good PS and no prior chemotherapy||• Offer docetaxel
• Offer abiraterone plus prednisone
• Offer ketoconazole plus steroid, mitoxantrone or radionuclide therapy to these patients who do not want or cannot have one of the standard therapies.
• Do NOT offer treatment with either estramustine or sipuleucel-T
|Symptomatic, mCRPC with poor PS and no prior docetaxel chemo||
• Offer treatment with ketoconazole plus steroid or radionuclide therapy to these patients who are unable or unwilling to receive abiraterone plus prednisone.
• Offer docetaxel or mitoxantrone chemotherapy in select cases, specifically when the PS is directly related to the cancer.
• Do NOT offer sipuleucel-T
|Symptomatic, mCRPC with good PS and prior docetaxel chemo||
• Offer treatment with abiraterone plus prednisone, cabazitaxel or enzalutamide. If the patient received abiraterone plus prednisone prior to docetaxel chemo, they should be offered cabazitaxel or enzalutamide.
• Offer ketoconazole plus steroid if abiraterone plus prednisone, cabazitaxel or enzalutamide is unavailable.
• Offer retreatment with docetaxel to these patients who were benefitting at the time of discontinuation (due to reversible side effects) of docetaxel treatment.
|Symptomatic, mCRPC with poor PS and prior docetaxel chemotherapy||
• Offer palliative care
• Alternatively, for selected patients, clinicians may offer treatment with abiraterone plus prednisone, enzalutamide, ketoconazole plus steroid or radionuclide therapy.
• Do NOT offer systemic chemotherapy or immunotherapy.
NOTE: The six index patients were defined by the presence or absence of metastatic disease, the severity of symptoms, the patient’s PS, and whether the patient has received prior treatment with docetaxel-based chemotherapy.
Abbreviations: mCRPC, metastatic castrate-resistant prostate cancer; PS, performance status.
Since the most common site for prostate cancer metastasis is the skeletal system, the guideline also makes key statements regarding bone health in patients with mCRPC:
- Clinicians should offer preventative treatment (e.g., supplemental calcium, vitamin D) 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.
“The fact remains,” Dr. Cookson said, “that mCRPC is the terminal stage of prostate cancer. As research continues in this area, we are hopeful that new developments well lead us closer to preventing the development of mCRPC.”
1. Castration-resistant Prostate Cancer: AUA Guidelines. The American Urologic Association. http://www.auanet.org/education/guidelines/castration-resistant-prostate-cancer.cfm. Accessed June 7, 2013.