Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

1. Among patients with localized low-risk prostate cancer (i.e., PSA <10 ng/ml and Gleason score <6 and <cT2a), what is the comparative effectiveness of androgen deprivation therapy (ADT) plus definitive external beam radiation therapy (EBRT) compared to EBRT alone? If ADT improves outcomes, for how long should ADT be administered and what is the optimal ADT regimen? 2. Among patients with localized intermediate-risk prostate cancer (i.e., PSA 10-20 ng/ml or Gleason score 7 or cT2b), what is the comparative effectiveness of ADT plus definitive EBRT compared to EBRT alone? If ADT improves outcomes, for how long should ADT be administered and what is the optimal ADT regimen? 3. Among patients with localized high-risk prostate cancer (i.e., PSA > 20 ng/ml or Gleason score 8-10 or > cT2c), what is the comparative effectiveness of ADT plus definitive EBRT compared to EBRT alone? If ADT improves outcomes, for how long should ADT be administered and what is the optimal ADT regimen? 4. Among patients receiving salvage prostate bed radiotherapy for a biochemical recurrence of prostate cancer after radical prostatectomy, what is the comparative effectiveness of ADT plus definitive EBRT compared to EBRT alone? If ADT improves outcomes, for how long should ADT be administered and what is the optimal ADT regimen?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

• ADT versus no ADT in combination with definitive EBRT among patients with low, intermediate, and high risk prostate cancer.

• ADT usually involves administration of a luteinizing hormone releasing hormone agonist (e.g., leuprolide, goserelin) with or without a non-steroidal anti-androgen (e.g., bicalutamide, flutamide).
• Alternatively, ADT may be achieved via bilateral orchiectomy.

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

• Adult men. In the United States, approximately 242,000 cases of prostate cancer will be diagnosed in 2013, and about 28,000 will die of the disease. The lifetime risk of prostate cancer among men living in the United States is estimated to be one in six. This topic nomination specifically focuses on patients diagnosed with localized prostate cancer, without evidence of regional or distant metastases.

Reference:

Siegel, Naishadham, & Jemal, Cancer Statistics, 2012. CA 2012; 62:10-29

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

Older men. Older men are at higher risk for the development of prostate cancer, which is rare in men younger than 40 years of age but common in men 60-69 (1 in 15) and in men 70 and older (1 in 8; Siegel et al, 2012).

• Black men. Black men are at higher risk (231 per 100,000) than white (143 per 100,000) or Hispanic men (127 per 100,000) for development of this disease. The age of onset in blacks is earlier than for comparative groups, and blacks are more likely to die of prostate cancer than men of other races (Siegel et al, 2012). Studies have found that blacks have higher PSA levels, Gleason scores, and disease stage at the time of diagnosis (Hoffman et al, JNCI 2001).
• Low income groups. Socioeconomic factors also play a role in the development of prostate cancer. Poor health literacy may increase the risk of more advanced stage at presentation, independently of race (Bennett et al, JCO 1998). Obesity, which is more common in low income populations, has been associated with prostate cancer aggressiveness (MacInnis & English, Cancer Causes Control 2006).

References:

Bennett et al, Relation between literacy, race, and stage of presentation among low-income patients with prostate cancer. J Clin Oncol 1998; 16:3101.

Harlan et al, Factors associated with initial therapy for clinically localized prostate cancer: prostate cancer outcomes study. J Natl Nancer Inst 2001; 93:1864.

Hoffman et al, Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study. J Natl Nancer Inst 2001; 93:388.

Krupski et al, Geographic and socioeconomic variation in the treatment of prostate cancer. J Clin Oncol 2005; 23: 7881.

MacInnis & English, Cancer Causes Control 2006; 17:989.

Siegel, Naishadham, & Jamal, Cancer Statistics, 2012. CA 2012; 62:10-29

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

• Improvements in overall survival

• Improvements in prostate cancer mortality
• Improvements in disease-free survival
• Improvements in prevention of malignant spread (i.e., distant metastasis)
• Better customization of treatment according to risk category and medical comorbidities

Multiple randomized controlled trials have investigated the role of neoadjuvant, concurrent, and adjuvant ADT in combination with EBRT in the definitive treatment of localized prostate cancer. The impact of ADT on an individual's survival depends on the risk stratum of his disease and potentially on his medical comorbidities (i.e., competing mortality risks). A comprehensive review of the literature would help our society create a guideline providing a clearer understanding of which patients should receive ADT in combination with EBRT, and for how long.

Describe any health-related risks, side effects, or harms that you are concerned about.

Side effects from ADT may include sexual dysfunction, osteopenia/osteoporosis, diabetes, cardiovascular disease, decreased muscle mass, increased fat, hot flashes, lack of energy, anemia, hepatotoxicity, gynecomastia, decreased penile and testicular size, thinning of body hair, and possibly decreased cognitive performance or depression.

Review of the available data will help clarify for which patients the benefits of ADT outweigh these potential risks.

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Cancer

AHRQ Priority Populations

• Low income groups
• Minority groups
• Elderly

Federal Health Care Program

• Medicaid
• Medicare

Importance

Describe why this topic is important.

Prostate cancer is the most common nondermatologic cancer in men and the most common cause of death from cancer in men over age 75. In an era of widespread PSA testing, most patients have clinically localized disease at diagnosis and are eligible for curative therapy. Many of these men elect EBRT. Numerous studies have interrogated the role of ADT in combination with EBRT, with varying results. A comprehensive review of the literature would elucidate the effect of adding ADT to EBRT with respect to survival, according to risk category of disease and other clinical features. It would also describe potential side effects, which can be significant. Current practice patterns are heterogeneous, and a more informed understanding of the role of ADT could influence the treatment and likelihood of cure of many thousands of patients. ADT does require a substantial financial cost, so it is important to understand from the perspective of medical resources for which patients ADT is appropriate.

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

The American Society for Radiation Oncology (ASTRO) intends to use the evidence report developed by AHRQ as the basis for a comprehensive, evidence-based, clinical practice guideline on the role of ADT in men receiving EBRT for prostate cancer. An AHRQ report would allow ASTRO to create a guideline product in a relatively short timeframe, as literature search, data extraction, and analysis would have already been completed according to the highest standards of systematic review. ASTRO guidelines are scientifically rigorous and evidence-based. With a staff of 5 full-time professionals and extensive consultant support, including both community and academic physicians considered experts in their respective disease sites, the ASTRO Guideline Committee develops guidelines efficiently and effectively. Guideline products are published in high impact journals and have been among the most widely read and downloaded articles from these journals. The ASTRO Guideline Committee hopes this evidence report will be the first of many collaborations between ASTRO and AHRQ in the creation of important guideline products for the oncology community.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

Numerous studies have investigated the role of ADT in combination with EBRT for prostate cancer, but variable results complicate interpretation. Significant differences in practice patterns reflect confusion over the available data as well as the presence of a preponderance of treatment options. The appropriateness of ADT in an individual patient depends on a variety of factors, including risk category and medical comorbidities. Creation of an evidence report and subsequent guideline product would help physicians make better informed decisions in what often represents a complicated clinical scenario.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

The ASTRO Guideline Committee, with the support of the ASTRO Board of Directors, produces regular guideline products and periodically updates existing guidelines. The creation of an AHRQ evidence report on this topic will enable ASTRO to develop a guideline to help physicians make better informed choices for their patients and reduce treatment inequalities in the community.

Describe the timeframe in which an answer to your question is needed.

It would be much appreciated if an AHRQ evidence report could be published in 2013.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

As described in the answer to question #3, black men are more likely to develop prostate cancer and more likely to die of prostate cancer, as they tend to acquire the disease at a younger age and at a more advanced stage. Moreover, studies suggest that blacks with localized prostate cancer receive aggressive treatment less often than either white or Hispanic men (Harlan et al, JNCI 2001; Krupski et al, JCO 2005), which may also contribute to increased mortality.

Socioeconomic factors may also influence the development and treatment of prostate cancer.

Medicare and Medicaid beneficiaries certainly develop prostate cancer. The elderly typically have Medicare coverage and the elderly are disproportionately affected by prostate cancer. Individuals with low incomes can be covered by both Medicare and Medicaid.

More uniform, evidence-based treatment of members of these populations could beneficially impact care.

References:

Harlan et al, Factors associated with initial therapy for clinically localized prostate cancer: prostate cancer outcomes study. J Natl Nancer Inst 2001; 93:1864.

Krupski et al, Geographic and socioeconomic variation in the treatment of prostate cancer. J Clin Oncol 2005; 23: 7881.

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

The ASTRO Guideline Committee, with the support of the ASTRO Board of Directors, produces regular guideline products and periodically updates existing guidelines. The creation of an AHRQ evidence report on this topic will enable ASTRO to develop a guideline to help physicians make better informed choices for their patients and reduce treatment inequalities in the community.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program

ASTRO staff

ASTRO staff