Final Research Plan
Prostate Cancer: Screening
December 21, 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 specific antigen.
1. What are the benefits of prostate 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, PSA density, and use of age-specific PSA thresholds for identification of prostate cancer?
4. What is the accuracy of using a prebiopsy prostate cancer risk calculator or magnetic resonance imaging (MRI), 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 in combination with a positive PSA-based screening test 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 in combination with a positive PSA-based screening test 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, family history, or Gleason grade/tumor risk category?
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, family history, or Gleason grade/tumor risk category?
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, presence of disabilities, health literacy, or other social determinants of health) 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, clinical risk category, presence of disabilities, health literacy, or social determinants of health?
4. What factors (e.g., race, ethnicity, age, socioeconomic status, educational attainment, presence of disabilities, health literacy, or other social determinants of health) 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 1–4 are designed to address other important health equity considerations.
The USPSTF intends to commission a decision model to accompany this evidence review.
| Category | Inclusion | Exclusion |
|---|---|---|
| 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 and men with a gene mutation associated with increased prostate cancer risk
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, and variable screening intervals)
KQ 3: Free PSA, use of age-specific PSA thresholds, PSA velocity, and PSA density 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; and genomic tests
KQ 4: Risk prediction instruments for diagnosis of any prostate cancer; risk prediction instruments without PSA; and 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 and 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, and area under the receiver operating characteristic curve); for detection of prostate cancer and for 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, and cognitive dysfunction); endocrinological effects (e.g., bone health, hot flashes, and gynecomastia); surgical complications; and long-term harms |
Other outcomes |
| Study Design |
KQs 1, 2, 4a, 4b, 5, 6: Randomized, controlled trials KQ 1: Cohort studies with concurrent control group and adjustment for confounders§ KQs 2, 4b, 5, 6: Cohort studies with concurrent control group and adjustment for confounders‖; large uncontrolled observational studies of harms¶ KQs 3, 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 specific antigen.
The draft Research Plan was posted on the USPSTF website for comment from October 12 to November 8, 2023. In response, the Research Plan was revised by editing the analytic framework for clarity and to separate PSA-based screening and diagnostic workup; adding PSA density as a PSA-based screening approach; adding Gleason grade/tumor risk category as a potential effect modifier of treatment; clarifying that the report will address diagnostic accuracy of PSA-based screening approaches for prostate cancer in general as well as for detection of clinically significant/high-grade cancer; clarifying that long-term harms will be addressed; and clarifying that other social determinants of health will be addressed as a potential factor associated with differences in uptake or utilization of screening, evaluation, and treatment.
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.
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.