AUA castration-resistant prostate cancer guideline seeks to clarify decision making

San Diego-The AUA has released its first-ever clinical practice guideline for castration-resistant prostate cancer (CRPC), and all urologists who care for men with advanced prostate cancer should familiarize themselves with its contents, said Michael S. Cookson, MD, who presented the new guideline at the AUA annual meeting in San Diego.

Dr. Cookson“In 2004, two landmark studies demonstrated docetaxel [Taxotere] extended the life of men with CRPC, and since then, four more agents for CRPC have been approved by the FDA based on demonstration of survival benefit. The greater availability of effective options makes decision making more complicated for clinicians and created a need for this guideline,” said Dr. Cookson, who served as the guideline panel chair and is vice-chairman and Hart Professor of Urologic Surgery at Vanderbilt University Medical Center, Nashville, TN.

The guideline statements were developed for six index patients intended to represent the most common scenarios encountered in clinical practice. CRPC patients are categorized by the presence or absence of metastases, the degree and severity of symptoms, their overall performance status, and whether or not they have received prior treatment with docetaxel (Taxotere) chemotherapy. Guideline statements for each of the index patients are rated as standard, recommendation, option, or expert opinion based on grading of the strength and quality of the evidence and the panel’s assessment of the benefits and harms of treatment. The statements are also formatted into a user-friendly algorithm that will be available in both a pocket guide and web-based format.

The following is a summary of the guideline statements for each index patient and respective statement type.

Index patient 1-asymptomatic with rising PSA, no metastases. Clinicians should recommend observation with continued androgen deprivation (recommendation).

“The reason for this recommendation is that none of the new agents have shown survival benefit for men with non-metastatic CRPC,” said Dr. Cookson.

Treatment with first-generation antiandrogens (flutamide [Eulexin], bicalutamide [Casodex], nilutamide [Nulandron]) or first-generation androgen synthesis inhibitors (ketoconazole+steroid) may be offered to select patients unwilling to accept observation (option).

These patients should not be offered systemic chemotherapy or immunotherapy outside of a clinical trial (recommendation).

Index patient 2-no or minimal symptoms, metastases, no prior docetaxel. Patients with good performance status should be offered abiraterone (ZYTIGA)+prednisone, docetaxel, or sipuleucel-T (Provenge) (standard).

“As a clinical principle, in the absence of comparative clinical trial data to direct sequencing, it is preferable to start with the least toxic agent, but decisions should also take into account ease of administration and patient preference,” Dr. Cookson said.

Patients who cannot or will not receive standard therapies may be offered first-generation antiandrogen therapy, ketoconazole+steroid, or even observation (option).

Index patient 3-symptomatic, metastases, good performance status, no prior docetaxel. These patients should be offered docetaxel (standard) or abiraterone+prednisone (option). Patients who do not want or cannot have either of these agents can be offered ketoconazole+steroid, mitoxantrone (Novantrone), or radionuclide therapy (option).

Neither estramustine (Emcyt, Estracit) nor sipuleucel-T should be offered (recommendation).

Index patient 4-symptomatic, metastases, poor performance status, no prior docetaxel. These patients may be offered abiraterone+prednisone (option) or either ketoconazole+steroid or radionuclide therapy if the patient is unwilling or unable to receive abiraterone+prednisone (option).

Docetaxel or mitoxantrone may be offered to patients whose poor performance status is directly related to their cancer (expert opinion).

Sipuleucel-T should not be offered (recommendation).

Index patient 5-symptomatic, metastases, good performance status, history of docetaxel. These patients should be offered abiraterone+prednisone (only if not received prior to docetaxel), cabazitaxel (Jevtana), or enzalutamide (Xtandi) (standard).

Ketoconazole+steroid is an alternative if any of the other agents is not available (option). Retreatment with docetaxel may be offered to select patients who discontinued treatment due to reversible side effects while demonstrating benefit (option).

Index patient 6-symptomatic, metastases, poor performance status, prior docetaxel. These men should be offered palliative care. Alternatively, select patients may also be offered abiraterone, enzalutamide, ketoconazole + steroid, or radionuclide therapy (expert opinion).

Bone health. The guideline also addresses bone health and states that all CRPC patients should be offered treatment with supplemental calcium and vitamin D to reduce the risk of fractures and skeletal-related events (recommendation). Select patients with bony metastases may be offered denosumab (Xgeva) and zoledronic acid (Zometa) (option).

On May 15, 2013, subsequent to Dr. Cookson’s presentation, the FDA approved radium Ra 223 dichloride (Xofigo) to treat men with symptomatic, metastatic CRPC that has spread to bones but not to other organs.

“The CRPC guideline encompassed published literature through Feb. 14, 2013, and was accepted for publication prior to FDA approval of radium Ra 223 dichloride. For this reason, the radionuclide is not included in the treatment recommendations, although it may now have a role in the treatment of certain patients included in the guideline. This document will be periodically updated to reflect the growing body of literature on castration-resistant prostate cancer.”UT