This is the current release of the guideline.

This guideline updates a previous version: Loblaw DA, Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ, Taplin ME, Vogelzang NJ, Wade JL Jr, Bennett CL, Scher HI. American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. J Clin Oncol 2004 Jul 15;22(14):2927-41.

Metastatic, recurrent, or progressive androgen-sensitive prostate cancer

Management
Treatment

Oncology
Radiation Oncology
Urology

Physicians

To update the 2004 American Society of Clinical Oncology (ASCO) guideline on initial hormonal management of androgen-sensitive, metastatic, recurrent, or progressive prostate cancer (PCa)

Men with metastatic, recurrent, or progressive androgen-sensitive prostate cancer

Standard Initial Treatment Options

1. Bilateral orchiectomy
2. Medical castration with luteinizing hormone releasing hormone (LHRH) agonists
3. Diethylstilbestrol (DES) (no longer commercially available in North America and is not recommended as a standard first-line treatment option)
4. Patient education/counseling

Castration Alternatives

1. Nonsteroidal antiandrogen monotherapy (e.g., flutamide, nilutamide, and bicalutamide)
2. Steroidal antiandrogen (not recommended as monotherapy)

Combination Therapy

Medical or surgical castration plus a nonsteroidal antiandrogen

Early Androgen Deprivation Therapy versus Deferred Therapy (early therapy not strongly recommended)

• Overall survival
• Progression-free survival
• Toxicity of treatment
• Time to treatment failure
• Disease progression
• Complications due to progression
• Cost-effectiveness
• Time off therapy
• Time to hormone resistance
• Quality of life

Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases

Seven randomized controlled trials (four new), one systematic review, one meta-analysis (new), one Markov model, and one delta-method 95% confidence interval (CI) procedure for active controlled trials (new) informed the guideline update.

Not stated

Not applicable

Review of Published Meta-Analyses
Systematic Review

Not stated

Expert Consensus

An evidence-based approach incorporating consensus by experts was the model used to create the recommendations. To this end, a subset of the original writing committee met via teleconference in February and March 2006 to consider the evidence for each of the 2004 recommendations. The guideline update was circulated in draft form to the full Expert Panel for review and approval. Suggestions from the Expert Panel were incorporated into the document, yielding a final set of recommendations.

Not applicable

One article was reviewed that showed early therapy is associated with higher costs and greater frequency of treatment-related adverse effects.

Internal Peer Review

The draft guideline was submitted to the American Society of Clinical Oncology (ASCO) Health Services Committee (HSC) for review and was endorsed in July 2006. The ASCO Board reviewed and approved the document in November 2006. Final text editing was performed by two of the guideline authors.

1. What are the standard initial treatment options?

   2006 Recommendation: Bilateral orchiectomy or medical castration with luteinizing hormone-releasing hormone (LHRH) agonists are the recommended initial treatments for metastatic prostate cancer. A full discussion between practitioner and patient should occur to determine which is best for the patient. Diethylstilbestrol (DES) should not be considered as a standard first-line treatment option and is no longer commercially available in North America.

2. Are antiandrogens as effective as other castration therapies?

   2006 Recommendation: Nonsteroidal antiandrogen (NSAA) monotherapy may be discussed as an alternative, but steroidal antiandrogen (AA) monotherapy should not be offered.

3. Is combined androgen blockade better than castration alone?

   2006 Recommendation: Combined androgen blockade (CAB) should be considered.

4. Does early androgen-deprivation treatment (ADT) improve outcomes over deferred therapy?

   2006 Recommendation: For patients with metastatic or progressive prostate cancer, there is a moderate decrease (17%) in relative risk (RR) for prostate cancer–specific mortality, a moderate increase (15%) in RR for non–prostate cancer–specific mortality, and no overall survival advantage for immediate institution of androgen-deprivation treatment (ADT) versus waiting until symptom onset for patients. Therefore, the Panel cannot make a strong recommendation for the early use of ADT. Prostate-specific antigen (PSA) kinetics and other metrics allow the identification of populations at high risk for prostate cancer–specific and overall mortality. Further studies must be completed to assess whether patients with adverse prognostic factors gain a survival advantage from immediate ADT. If a patient decides to wait until symptoms for ADT, he should have regular visits for monitoring. For patients with recurrent disease, clinical trials should be considered if available.

5. What is the role of intermittent androgen blockade?

   2006 Recommendation: Currently, data are insufficient to support the use of intermittent androgen blockade outside of clinical trials.

A clinical algorithm is provided for the initial hormonal management of androgen-sensitive advanced cancer (see "Availability of Companion Documents" field in this summary).

The recommendations are supported by randomized controlled trials, a systematic review, a meta-analysis, one Markov model, and one delta-method 95% confidence interval (CI) procedure for active controlled trials.

Appropriate management of androgen-sensitive, metastatic, recurrent, or progressive prostate cancer

• Table 3 in the original guideline document provides a full list of adverse drug reactions seen in a randomized controlled trial of patients receiving an LHRH agonist and then either bicalutamide or placebo.
• Early therapy is associated with higher costs and greater frequency of treatment-related adverse effects. Deferred treatment risks the development of hormone independence in the tumor as well as serious complications such as spinal cord complications. The effects of these complications occurring during the treatment deferral period might not be completely reversible.

It is important to realize that many management questions have not been comprehensively addressed in randomized trials and guidelines cannot always account for individual variation among patients. A guideline is not intended to supplant physician judgment with respect to particular patients or special clinical situations and cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same results. Accordingly, the American Society of Clinical Oncology (ASCO) considers adherence to this guideline to be voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient's individual circumstances. In addition, the guideline describes administration of therapies in clinical practice; it cannot be assumed to apply to interventions performed in the context of clinical trials, given that clinical studies are designed to test innovative and novel therapies in a disease and setting for which better therapy is needed. Because guideline development involves a review and synthesis of the latest literature, a practice guideline also serves to identify important questions for further research and those settings in which investigational therapy should be considered.

An implementation strategy was not provided.

Living with Illness

Effectiveness
Patient-centeredness

Not applicable: The guideline was not adapted from another source.

2004 Jun 7 (revised 2007 Apr)

American Society of Clinical Oncology - Medical Specialty Society

American Society of Clinical Oncology (ASCO)

American Society of Clinical Oncology (ASCO) Metastatic Prostate Cancer Expert Panel

Primary Authors: D. Andrew Loblaw; Katherine S. Virgo; Robert Nam; Mark R. Somerfield; Edgar Ben-Josef; David S. Mendelson; Richard Middleton; Stewart A. Sharp; Thomas J. Smith; James Talcott; Maryellen Taplin; Nicholas J. Vogelzang; James L. Wade III; Charles L. Bennett; Howard I. Scher

ASCO Metastatic Prostrate Cancer Expert Panel: Howard I. Scher, MD, Cochair Memorial Sloan-Kettering Cancer Center; Charles L. Bennett, MD, PhD, Cochair VA Chicago Health Care System-Lakeside and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University; Edgar Ben-Josef, MD, Wayne State University; D. Andrew Loblaw, MD, MSc, Sunnybrook Health Sciences Centre; David S. Mendelson, MD, Premiere Oncology of Arizona; Richard Middleton, MD, University of Utah Medical School; Robert Nam, MD, MSc, Sunnybrook Health Sciences Centre; Thomas J. Smith, MD, Massey Cancer Center, Medical College of Virginia; Stewart A. Sharp, MD, Danville Hematology & Oncology, Inc; James Talcott, MD,MPH, Massachusetts General Hospital; Maryellen Taplin, MD, Dana-Farber Cancer Institute; Katherine S. Virgo, PhD, Saint Louis University & Department of Veterans' Affairs Medical Center; Nicholas J. Vogelzang, MD, University of Chicago Cancer Research Center; James L. Wade III, MD, Cancer Care Specialists of Central Illinois

Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest.

No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A Leadership: N/A Consultant: D. Andrew Loblaw, Astra Zeneca; Nicholas J. Vogelzang, Sanofi Aventis; Charles L. Bennett, Sanofi, Millenium Stock: N/A Honoraria: D. Andrew Loblaw, Astra Zeneca; James Talcott, Dendreon; Maryellen Taplin, Astra Zeneca; Nicholas J. Vogelzang, Astra Zeneca Research Funds: D. Andrew Loblaw, Astra Zeneca; Nicholas J. Vogelzang, Astra Zeneca; Charles L. Bennett, Amgen, Sanofi Testimony: N/A Other: D. Andrew Loblaw, Astra Zeneca, Sanofi-Aventis

This is the current release of the guideline.

This guideline updates a previous version: Loblaw DA, Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, Middleton R, Porterfield H, Sharp SA, Smith TJ, Taplin ME, Vogelzang NJ, Wade JL Jr, Bennett CL, Scher HI. American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. J Clin Oncol 2004 Jul 15;22(14):2927-41.

This NGC summary was completed by ECRI on August 11, 2004. The information was verified by the guideline developer on August 13, 2004. This NGC summary was updated by ECRI Institute on June 26, 2007. The updated information was verified by the guideline developer on July 16, 2007.

This summary is based on the original guideline, which is subject to the American Society of Clinical Oncology's copyright restrictions.