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## Complete Summary

#### GUIDELINE TITLE

Initial hormonal management of androgen-sensitive metastatic, recurrent,
or progressive prostate cancer: 2006 update of an American Society of
Clinical Oncology practice guideline.

#### BIBLIOGRAPHIC SOURCE(S)

Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS,
Middleton R, Sharp SA, Smith TJ, Talcott J, Taplin M, Vogelzang NJ, Wade
JL 3rd, Bennett CL, Scher HI, American Society of Clinical Oncology.
Initial hormonal management of androgen-sensitive metastatic, recurrent,
or progressive prostate cancer: 2006 update of an American Society of
Clinical Oncology practice guideline. J Clin Oncol 2007 Apr
20;25(12):1596-605. \[29 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17404365)

#### GUIDELINE STATUS

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.

### COMPLETE SUMMARY CONTENT

 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Metastatic, recurrent, or progressive androgen-sensitive prostate cancer

#### GUIDELINE CATEGORY

Management\
Treatment

#### CLINICAL SPECIALTY

Oncology\
Radiation Oncology\
Urology

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

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)

#### TARGET POPULATION

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

#### INTERVENTIONS AND PRACTICES CONSIDERED

**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)

#### MAJOR OUTCOMES CONSIDERED

-   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

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

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

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

**Literature Review and Data Collection**

For the 2006 update, the MEDLINE database (January 2003 through March
2006; National Library of Medicine, Bethesda, MD) was searched to
identify relevant information from the published literature. A series of
searches was conducted using the medical subject headings \"prostatic
neoplasms\" and \"androgen antagonists,\" and the text words
\"intermittent,\" \"combined androgen,\" and \"metastatic.\" These terms
were combined with the following study design-related subject headings
or text words: \"meta-analysis,\" \"systematic,\" trial,\" and
\"randomized.\" Search results were limited to human studies and
English-language articles.

In addition, the Cochrane Database of Systematic Reviews was searched
using the phrase \"prostate cancer,\" and directed searches were made of
the reference lists from primary articles. Authors were contacted for
clarification where needed. The Physician Data Query clinical trials
database (<http://www.cancer.gov/search/clinical_trials/>) was searched
for ongoing clinical trials in the identified subject areas.

**Inclusion and Exclusion Criteria**

Table 1 in the original guideline document describes the details of the
inclusion criteria and outcome variables for each question addressed in
this guideline. For each guideline question, letters, editorials, and
articles published in a language other than English were not considered.
In addition, for questions 4 (early vs. deferred androgen deprivation
therapy \[ADT\]) and 5 (intermittent versus continuous ADT), the
following were excluded:

1.  Participants previously treated with hormonal therapy

2.  Randomized clinical trials targeting men undergoing radiation as
    primary therapy

3.  Nonrandomized prospective studies

4.  Retrospective studies

5.  Trials or trial arms that used diethylstilbestrol

#### NUMBER OF SOURCE DOCUMENTS

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.

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not applicable

#### METHODS USED TO ANALYZE THE EVIDENCE

Review of Published Meta-Analyses\
Systematic Review

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

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.

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

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

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

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.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

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.

#### CLINICAL ALGORITHM(S)

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

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

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.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

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

#### POTENTIAL HARMS

-   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.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

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.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Clinical Algorithm\
Patient Resources\
Personal Digital Assistant (PDA) Downloads\
Slide Presentation

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Living with Illness

#### IOM DOMAIN

Effectiveness\
Patient-centeredness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS,
Middleton R, Sharp SA, Smith TJ, Talcott J, Taplin M, Vogelzang NJ, Wade
JL 3rd, Bennett CL, Scher HI, American Society of Clinical Oncology.
Initial hormonal management of androgen-sensitive metastatic, recurrent,
or progressive prostate cancer: 2006 update of an American Society of
Clinical Oncology practice guideline. J Clin Oncol 2007 Apr
20;25(12):1596-605. \[29 references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17404365)

#### ADAPTATION

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

#### DATE RELEASED

2004 Jun 7 (revised 2007 Apr)

#### GUIDELINE DEVELOPER(S)

American Society of Clinical Oncology - Medical Specialty Society

#### SOURCE(S) OF FUNDING

American Society of Clinical Oncology (ASCO)

#### GUIDELINE COMMITTEE

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

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

*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

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

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

#### GUIDELINE STATUS

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.

#### GUIDELINE AVAILABILITY

Electronic copies: Available in Portable Document Format (PDF) from the
[American Society of Clinical Oncology (ASCO) Web
site](http://jco.ascopubs.org/cgi/content/full/25/12/1596).

Print copies: Available from American Society of Clinical Oncology,
Cancer Policy and Clinical Affairs, 1900 Duke Street, Suite 200,
Alexandria, VA 22314; E-mail: <guidelines@asco.org>.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following are available:

-   American Society of Clinical Oncology (ASCO) treatment algorithm for
    the initial hormonal management of androgen-sensitive advanced
    cancer: 2007 update. Available from the [ASCO Web
    site](http://www.asco.org/ASCO/Downloads/Cancer Policy and Clinical Affairs/Clinical Affairs (derivative products)/Andro-Sen Treatment Algorithm 2.pdf).
    See the related QualityTool summary on the [Health Care Innovations
    Exchange Web site](http://innovations.ahrq.gov/content.aspx?id=425).

-   Initial hormonal management of androgen-sensitive metastatic,
    recurrent, or progressive prostate cancer: 2007 update. Slide set.
    Available from the [ASCO Web
    site](http://www.asco.org/ASCO/Downloads/Cancer Policy and Clinical Affairs/Clinical Affairs (derivative products)/Andro-Sen slides 4.5.07.pdf).
    See the related QualityTool summary on the [Health Care Innovations
    Exchange Web site](http://innovations.ahrq.gov/content.aspx?id=604).

-   ASCO 2007 guideline update: recommendations for the initial hormonal
    management of androgen-sensitive metastatic, recurrent, or
    progressive prostate cancer. Revisions Table. Available from the
    [ASCO Web
    site](http://www.asco.org/ASCO/Downloads/Cancer Policy and Clinical Affairs/Clinical Affairs (derivative products)/Andro-Sen Revisions Table 2.pdf).
    See the related QualityTool summary on the [Health Care Innovations
    Exchange Web site](http://innovations.ahrq.gov/content.aspx?id=413).

Guidelines are available for Personal Digital Assistant (PDA) download
from the [ASCO Web
site](http://www.asco.org/ASCO/Downloads+%26+Technology/PDA+Services).

#### PATIENT RESOURCES

The following is available:

-   American Society of Clinical Oncology (ASCO) patient guide: hormone
    therapy for advanced prostate cancer. Available from the [Cancer.Net
    Web
    site](http://www.cancer.net/portal/site/patient/menuitem.169f5d85214941ccfd748f68ee37a01d/?vgnextoid=33d241eca8daa010VgnVCM100000ed730ad1RCRD).
    See the related QualityTool summary on the [Health Care Innovations
    Exchange Web site](http://innovations.ahrq.gov/content.aspx?id=427).

Please note: This patient information is intended to provide health
professionals with information to share with their patients to help them
better understand their health and their diagnosed disorders. By
providing access to this patient information, it is not the intention of
NGC to provide specific medical advice for particular patients. Rather
we urge patients and their representatives to review this material and
then to consult with a licensed health professional for evaluation of
treatment options suitable for them as well as for diagnosis and answers
to their personal medical questions. This patient information has been
derived and prepared from a guideline for health care professionals
included on NGC by the authors or publishers of that original guideline.
The patient information is not reviewed by NGC to establish whether or
not it accurately reflects the original guideline\'s content.

#### NGC STATUS

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.

#### COPYRIGHT STATEMENT

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

### DISCLAIMER

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008