Draft Research Plan
Prostate Cancer: Screening
October 12, 2023
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.
*Active surveillance and watchful waiting are typically compared to more active treatments in trials.
†Including harms related to overdiagnosis and overtreatment.
Abbreviation: PSA=prostate cancer–specific antigen.
1. What are the benefits of prostate cancer–specific antigen (PSA)-based screening for prostate cancer vs. no screening or usual care on short- or long-term prostate cancer mortality, incidence of metastatic prostate cancer, all-cause mortality, quality of life, and function?
1a. Do the benefits of PSA-based screening vary in populations defined by age, race, ethnicity, or family history?
2. What are the harms of PSA-based screening for prostate cancer vs. no screening or usual care, including harms of associated diagnostic followup?
2a. Do the harms of PSA-based screening for prostate cancer vary in populations defined by age, race, ethnicity, or family history?
3. What is the diagnostic accuracy of PSA-based screening using free PSA, PSA velocity, and use of age-specific PSA thresholds for identification of prostate cancer?
4. What is the accuracy of a prebiopsy prostate cancer risk calculator or MRI (magnetic resonance imaging), in combination with a positive PSA-based screening test, for identification of men with clinically significant prostate cancer (i.e., cancer that is more likely to cause symptoms or lead to advanced disease)?
4a. What is the effect of using a prebiopsy prostate cancer risk calculator or MRI on prostate cancer biopsy rates compared to PSA-based screening alone?
4b. What is the effect of using a prebiopsy prostate cancer risk calculator or MRI on prostate cancer morbidity and mortality, quality of life, and function compared to PSA-based screening alone?
5. What are the benefits of curative treatment approaches for screen-detected or early-stage prostate cancer vs. active surveillance or watchful waiting on prostate cancer mortality, incidence of metastatic prostate cancer, all-cause mortality, quality of life, and function?
5a. Do the benefits of treatment vary in populations defined by age, race, ethnicity, or family history?
6. What are the harms of curative treatment approaches for screen-detected or early-stage prostate cancer vs. active surveillance or watchful waiting?
6a. Do the harms vary in populations defined by age, race, ethnicity, or family history?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
1. What factors (e.g., race, ethnicity, age, socioeconomic status, educational attainment, or health literacy) are associated with differences in uptake of prostate cancer screening and disparities in utilization of risk-adapted approaches?
2. What is the effectiveness of primary care–based interventions to reduce differences in uptake of prostate cancer screening and disparities in utilization of risk-adapted approaches?
3. How often are the various treatment approaches currently performed in U.S. men with prostate cancer detected by PSA-based screening (i.e., what percentage of men initially choose active surveillance or watchful waiting vs. curative treatments such as surgery, radiation, or ablative therapy)?
3a. How does the use of various treatment approaches vary by age, race, ethnicity, and clinical risk category?
4. What factors (e.g., race, ethnicity, age, socioeconomic status, educational attainment, or health literacy) are associated with differences in utilization of treatments for screen-detected or early-stage prostate cancer?
5. Can patient- or physician-level interventions (e.g., decision aids) successfully align prostate cancer screening and treatment decisions with patients’ informed personal preferences?
To the extent possible, we plan to describe the participant characteristics and major intervention components of the included studies. Data on population characteristics will help us explore the degree to which the findings are broadly representative of the U.S. population, including individuals in groups based on age; sex and gender; racial, ethnic, and cultural identity; socioeconomic status; and geographic region. Evidence will be evaluated to determine if there are common components of efficacious interventions and, to the extent possible, whether interventions tailored to specific groups tend to have larger effect sizes than those that are not tailored. As part of our effort to address health equity, we will search for and highlight interventions that demonstrate effectiveness in groups of individuals who historically have higher rates of prostate cancer and in traditionally stigmatized or underrepresented groups. Additionally, the proposed Contextual Questions 1 to 4 are designed to address other important health equity considerations.
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.
| Category | Included | Excluded |
|---|---|---|
| Populations | KQs 1-3: Asymptomatic men* without a prior diagnosis of prostate cancer
KQ 4: Asymptomatic men with a positive PSA-based screening test KQs 5, 6: Men with screen-detected or non-screen-detected, early-stage prostate cancer (defined as stage I or II) |
KQs 1-4: Symptomatic men
KQs 5, 6: Men with later-stage, non-screen-detected prostate cancer†; men with refractory, hormone refractory, or recurrent prostate cancer |
| Settings | Primary care or specialty care settings in countries categorized as “Very High” on the Human Development Index (as defined by the United Nations Development Programme) | Countries not categorized as “Very High” on the Human Development Index |
| Interventions | KQs 1, 2: PSA-based screening (single-threshold total PSA, free PSA, use of age-specific PSA thresholds, PSA velocity, variable screening intervals)
KQ 3: Free PSA, use of age-specific PSA thresholds, and PSA velocity KQ 4: Post-PSA, prebiopsy prostate cancer risk calculator to predict clinically important prostate cancer and prebiopsy multiparametric MRI KQs 5, 6:
|
KQs 1-3: Non–PSA-based methods of screening for prostate cancer, performed alone (e.g., digital rectal examination), urine biomarkers, or genomic tests
KQ 4: Risk prediction instruments for diagnosis of any prostate cancer; risk prediction instruments without PSA; risk prediction instruments that include urinary biomarkers, other serum biomarkers, genomic instruments, or advanced imaging KQs 5, 6: Chemotherapy and hormone therapy (typically used for the treatment of later-stage cancer) |
| Comparisons | KQs 1, 2: Usual care; no screening
KQ 3: Reference standard for prostate cancer KQ 4: Reference standard for clinically important prostate cancer KQs 4a, 4b: PSA-based screening without a prostate cancer risk calculator KQs 5, 6: Active surveillance or watchful waiting |
Other comparisons |
| Outcomes | KQs 1, 4b, 5: Prostate cancer mortality; all-cause mortality; prostate cancer–specific morbidity (i.e., bone pain from metastases, urinary obstruction); functioning, quality of life, and incidence of advanced-stage cancer (including metastatic prostate cancer)
KQ 2: Physical or psychological harms of screening or biopsy; overdiagnosis KQs 3, 4: Test performance (sensitivity, specificity, area under the receiver operating characteristic curve); detection of clinically significant or high-grade prostate cancer (KQ 4) KQ 4a: Biopsy rate KQ 6: Bowel, urinary, and sexual dysfunction; psychological effects (e.g., mental status, depression, cognitive dysfunction); endocrinological effects (e.g., bone health, hot flashes, gynecomastia); and surgical complications |
Other outcomes |
| Study Design |
KQs 1, 2, 4a, 4b, 5, and 6: Randomized, controlled trials KQ 1: Cohort studies with concurrent control group and adjustment for confounders§ KQs 2, 4b, 5, and 6: Cohort studies with concurrent control group and adjustment for confounders‖; large uncontrolled observational studies of harms¶ KQs 3 and 4: Cross-sectional and cohort studies reporting diagnostic accuracy |
Other study designs |
* We will consider asymptomatic men to be those without symptoms that are highly suspicious for prostate cancer.
† Treatments for men with later-stage prostate cancer (stages III or IV) differ from those for men with early-stage prostate cancer (stages I or II); large, population-based PSA-based screening studies1,2 have primarily detected early-stage cancer (90% to 96% of cancers detected).
‡Active surveillance and watchful waiting are typically compared to more active treatments in trials.
§ For populations not addressed well in randomized, controlled trials.
║Sample size of >100.
¶ Sample size of at least 1,000; uncontrolled studies only eligible if randomized, controlled trials and cohort studies are not available.
Abbreviations: KQ=key question; MRI=magnetic resonance imaging; PSA=prostate cancer–specific antigen.
1. Andriole GL, Crawford ED, Grubb RL 3rd, et al; PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009;360(13):1310-1319. doi: 10.1056/NEJMoa0810696. PMID: 19297565.
2. Schröder FH, Hugosson J, Roobol MJ, et al; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320-1328. doi: 10.1056/NEJMoa0810084. PMID: 19297566.