Draft Research Plan
Draft Research Plan for Prostate Cancer: Screening
This opportunity for public comment expired on November 26, 2015 at 8:00 PM EST
Note: This is a Draft Research Plan. This draft is distributed solely for the purpose of receiving public input. It has not been disseminated otherwise by the USPSTF. The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Draft: Proposed Analytic Framework
The figure shows the proposed analytic framework, which depicts the 5 key questions for the systematic review for screening for prostate cancer. Key question 1 addresses the effectiveness of screening with the prostate-specific antigen (PSA) test in reducing mortality and morbidity from prostate cancer. Key question 2 addresses the harms of PSA-based screening. Key question 3 addresses the effectiveness of treatment of early-stage or screen-detected prostate cancer in reducing morbidity and mortality. Key question 4 addresses the harms of treatment of early-stage or screen-detected prostate cancer. Finally, key question 5 addresses the effectiveness of prostate cancer risk calculators combined with PSA testing to increase the detection of clinically significant prostate cancer (i.e., cancer that is more likely to cause symptoms or lead to advanced disease).
Draft: Proposed Key Questions to Be Systematically Reviewed
- Does screening for prostate cancer with the prostate-specific antigen (PSA) test, as a single threshold test or as a function of multiple tests over time, reduce short- or long-term morbidity*, prostate cancer–specific mortality, and/or all-cause mortality? Does the effectiveness of screening vary by risk factor (age, race/ethnicity, family history, and comorbid conditions)?
- What are the harms of PSA-based screening for prostate cancer?
- Does treatment of early-stage or screen-detected prostate cancer reduce morbidity* and/or mortality? Do these benefits of treatment vary by risk factor (age, race/ethnicity, family history, and comorbid conditions)?
- What are the harms of treatment of early-stage or screen-detected prostate cancer? Do these harms of treatment vary by risk factor (age, race/ethnicity, family history, and comorbid conditions)?
- Does the use of prostate cancer risk calculators, in combination with PSA testing, increase the positive predictive value of biopsy for the detection of clinically significant prostate cancer (i.e., those cases that are more likely to cause symptoms or lead to advanced disease)?
* Morbidity includes diagnosis of stage IV prostate cancer with attendant symptoms related to pain, bony metastases, complications due to late-stage disease, and health-related quality of life.
Draft: Proposed Contextual Questions
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- How often do men in the United States with prostate cancer detected by PSA testing receive treatment (i.e., what percentage of men initially choose watchful waiting vs. surgery, radiation, or cryotherapy)?
- What are the treatment preferences of men in the United States with prostate cancer detected by PSA testing (i.e., what percentage of men prefer active surveillance or watchful waiting vs. surgery, radiation, or cryotherapy)?
- What newer tests or testing strategies (such as different PSA thresholds or genomic or urine testing) can help identify prostate cancer that is more or less likely to cause symptoms or lead to advanced disease? What are the test performance characteristics of such tests?
Draft: Proposed Research Approach
The proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).
|Population||KQs 1, 2, 5: Asymptomatic men*
KQs 3, 4: Men with screen-detected or early-stage prostate cancer (defined as stage I or II)
|KQs 1, 2, 5: Symptomatic men
KQs 3, 4: Men with later-stage prostate cancer†; men with refractory, hormone refractory, or recurrent prostate cancer
|Setting||Primary care settings; studies conducted in countries categorized as “Very High” on the Human Development Index (as defined by the United Nations Development Programme)||Specialty care settings; studies conducted in countries not categorized as “Very High” on the Human Development Index|
|Interventions||KQs 1, 2: PSA-based screening (single-threshold PSA testing, age-adjusted thresholds, velocity, and doubling time)
KQs 3, 4: Surgery (radical prostatectomy, including different surgical techniques, such as nerve sparing and robotics); androgen deprivation therapy (via luteinizing hormone-releasing hormone agonists, antiandrogen therapy, and/or orchiectomy); radiation therapy (external-beam radiation therapy, proton beam therapy, brachytherapy, and combination therapies); cryotherapy; ultrasonography (high-intensity focused ultrasonography); watchful waiting; active surveillance
KQ 5: Risk prediction models to predict clinically important prostate cancer
|KQs 1, 2: Other methods of prostate cancer screening; digital rectal examination alone
KQs 3, 4: Chemotherapy (typically used for later-stage cancer)
KQ 5: Risk prediction models for any prostate cancer
|Comparisons||KQs 1, 2: Usual care; no screening
KQs 3, 4: No treatmentKQ 5: Screening with PSA testing only; usual care
|Outcomes||KQ 1: Prostate cancer mortality; all-cause mortality; prostate cancer–specific morbidity (i.e., bone pain from metastases, urinary obstruction); incidence of advanced stage cancer
KQ 2: False-positive results; physical harms of screening or biopsy; psychological harms; overdiagnosis
KQs 3, 4: Mortality (overall and disease-specific); quality of life (overall and disease-specific); functioning (overall and disease-specific); bowel, urinary, and sexual dysfunction; psychological effects (e.g., mental status, depression, and cognitive dysfunction); endocrinological effects (e.g., bone health, hot flashes, and gynecomastia); surgical complications
KQ 5: Clinically significant or high-grade prostate cancer; positive predictive value of biopsy
|Duration||KQ 1: Long-term prostate cancer mortality, long-term all-cause mortality
KQs 3, 4: 30 days for perioperative complications; >12 months for other harms
|Study Designs||KQ 1: Randomized, controlled trials; systematic reviews (of included study designs); meta analyses
KQs 2–5: Randomized, controlled trials; cohort studies; uncontrolled observational studies of harms‡
|Other study designs|
|Study Quality||Good- and fair-quality studies||Poor-quality studies|
|Language||English language||Languages other than English|
|Timeframe||1/1/2011 to present§||Published before 1/1/2011|
* Asymptomatic men will be considered as those without symptoms that are highly suspicious for prostate cancer. Many older men have chronic but stable lower urinary track symptoms (e.g., due to benign prostate hyperplasia) that are not generally associated with an increased risk for prostate cancer.1
† Treatments for later-stage prostate cancer (stages III or IV) differ from those for early-stage prostate cancer (stages I or II); large, population-based PSA screening studies have primarily detected early-stage cancer (90% to 96% of cancers detected).2, 3
‡ Sample size of at least 1,000 men; smaller samples sizes will be included only if randomized, controlled trials, cohort studies, and larger uncontrolled studies are not available.
§ Although this review’s search dates will cover the years 2011 through the present, the USPSTF will consider evidence from older trials included in prior systematic reviews. That is, the evidence review will primarily search for new studies or updates of previous trials, but the USPSTF, in making its recommendation, will consider the totality of evidence available, not just studies published since 2011.
1. Akaza H, Kanetake H, Tsukamoto T, Miyanaga N, Sakai H, Masumori N, et al. Efficacy and safety of dutasteride on prostate cancer risk reduction in Asian men: the results from the REDUCE study. Jpn J Clin Oncol. 2011;41(3):417-23.
2. Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310-9.
3. Schroder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320-8.
Internet Citation: Draft Research Plan: Prostate Cancer: Screening. U.S. Preventive Services Task Force. October 2015.