Unabridged version of this Guideline [pdf]
Early Detection Figures 1-3 [pdf]

To Cite:

Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part I: prostate cancer screening. J Urol. 2023;210(1):45-53.

Wei JT, Barocas D, Carlsson S, et al. Early detection of prostate cancer: AUA/SUO guideline part II: considerations for a prostate biopsy. J Urol. 2023;210(1):54-63.

John T. Wei, MD, MS; Daniel Barocas, MD; Sigrid Carlsson, MD, PhD, MPH; Fergus Coakley, MD; Scott Eggener, MD; Ruth Etzioni, PhD; Samson W. Fine, MD; Misop Han, MD; Badrinath R. Konety, MD; Martin Miner, MD; Kelvin Moses, MD, PhD; Merel G. Nissenberg, JD; Peter A. Pinto, MD; Simpa S. Salami, MD, MPH; Lesley Souter, PhD; Ian M. Thompson, MD; Daniel W. Lin, MD

SUMMARY

Purpose

The recommendations discussed in the early detection of prostate cancer provide a framework to facilitate clinical decision-making in the implementation of prostate cancer screening and follow-up.

Methodology

The systematic review of this guideline was based on searches in Ovid MEDLINE and Embase and Cochrane Database of Systematic Reviews (January 1, 2000 – November 21, 2022). Searches were supplemented by reviewing reference lists of relevant articles. Criteria for inclusion and exclusion of studies were based on the Key Questions and the populations, interventions, comparators, outcomes, timing, types of studies and settings (PICOTS) of interest. The target population was persons without a diagnosis of prostate cancer undergoing prostate-specific antigen (PSA) screening, or patients without prostate cancer who have a suspicious finding indicating possible clinically significant prostate cancer and are undergoing or considering an initial or repeat biopsy.

GUIDELINE STATEMENTS

PSA Screening

1. Clinicians should engage in shared decision-making (SDM) with people for whom prostate cancer screening would be appropriate and proceed based on a person’s values and preferences. (Clinical Principle)
2. When screening for prostate cancer, clinicians should use PSA as the first screening test. (Strong Recommendation; Evidence Level: Grade A)
3. For people with a newly elevated PSA, clinicians should repeat the PSA prior to a secondary biomarker, imaging, or biopsy. (Expert Opinion)
4. Clinicians may begin prostate cancer screening and offer a baseline PSA test to people between ages 45 to 50 years. (Conditional Recommendation; Evidence Level: Grade B)
5. Clinicians should offer prostate cancer screening beginning at age 40 to 45 years for people at increased risk of developing prostate cancer based on the following factors: Black ancestry, germline mutations, strong family history of prostate cancer. (Strong Recommendation; Evidence Level: Grade B)
6. Clinicians should offer regular prostate cancer screening every 2 to 4 years to people aged 50 to 69 years. (Strong Recommendation; Evidence Level: Grade A)
7. Clinicians may personalize the re-screening interval, or decide to discontinue screening, based on patient preference, age, PSA, prostate cancer risk, life expectancy, and general health following SDM. (Conditional Recommendation; Evidence Level: Grade B)
8. Clinicians may use digital rectal exam (DRE) alongside PSA to establish risk of clinically significant prostate cancer. (Conditional Recommendation; Evidence Level: Grade C)
9. For people undergoing prostate cancer screening, clinicians should not use PSA velocity as the sole indication for a secondary biomarker, imaging, or biopsy. (Strong Recommendation; Evidence Level: Grade B)
10. Clinicians and patients may use validated risk calculators to inform the SDM process regarding prostate biopsy. (Conditional Recommendation; Evidence Level: Grade B)
11. When the risk of clinically significant prostate cancer is sufficiently low based on available clinical, laboratory, and imaging data, clinicians and patients may forgo near-term prostate biopsy. (Clinical Principle)

Initial Biopsy

12. Clinicians should inform patients undergoing a prostate biopsy that there is a risk of identifying a cancer with a sufficiently low risk of mortality that could safely be monitored with active surveillance (AS) rather than treated. (Clinical Principle)
13. Clinicians may use magnetic resonance imaging (MRI) prior to initial biopsy to increase the detection of Grade Group (GG) 2+ prostate cancer. (Conditional Recommendation; Evidence Level: Grade B)
14. Radiologists should utilize PI-RADS in the reporting of multi-parametric MRI (mpMRI) imaging. (Moderate Recommendation; Evidence Level: Grade C)
15. For biopsy-naïve patients who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy. (Moderate Recommendation [targeted biopsies]/Conditional Recommendation [systematic template biopsy]; Evidence Level: Grade C)
16. For patients with both an absence of suspicious findings on MRI and an elevated risk for GG2+ prostate cancer, clinicians should proceed with a systematic biopsy. (Moderate Recommendation; Evidence Level: Grade C)
17. Clinicians may use adjunctive urine or serum markers when further risk stratification would influence the decision regarding whether to proceed with biopsy. (Conditional Recommendation; Evidence Level: Grade C)
18. For patients with a PSA > 50 ng/mL and no clinical concerns for infection or other cause for increased PSA (e.g., recent prostate instrumentation), clinicians may omit a prostate biopsy in cases where biopsy poses significant risk or where the need for prostate cancer treatment is urgent (e.g., impending spinal cord compression). (Expert Opinion)

Repeat Biopsy

19. Clinicians should communicate with patients following biopsy to review biopsy results, reassess risk of undetected or future development of GG2+ disease, and mutually decide whether to discontinue screening, continue screening, or perform adjunctive testing for early reassessment of risk. (Clinical Principle)
20. Clinicians should not discontinue prostate cancer screening based solely on a negative prostate biopsy. (Strong Recommendation; Evidence Level: Grade C)
21. After a negative biopsy, clinicians should not solely use a PSA threshold to decide whether to repeat the biopsy. (Strong Recommendation; Evidence Level: Grade B)
22. If the clinician and patient decide to continue screening after a negative biopsy, clinicians should re-evaluate the patient within the normal screening interval (two to four years) or sooner, depending on risk of clinically significant prostate cancer and life expectancy. (Clinical Principle)
23. At the time of re-evaluation after negative biopsy, clinicians should use a risk assessment tool that incorporates the protective effect of prior negative biopsy. (Strong Recommendation; Evidence Level: Grade B)
24. After a negative initial biopsy in patients with low probability for harboring GG2+ prostate cancer, clinicians should not reflexively perform biomarker testing. (Clinical Principle)
25. After a negative biopsy, clinicians may use blood, urine, or tissue-based biomarkers selectively for further risk stratification if results are likely to influence the decision regarding repeat biopsy or otherwise substantively change the patient’s management. (Conditional Recommendation; Evidence Level: Grade C)
26. In patients with focal (one core) high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy, clinicians should not perform immediate repeat biopsy. (Moderate Recommendation; Evidence Level: Grade C)
27. In patients with multifocal HGPIN, clinicians may proceed with additional risk evaluation, guided by PSA/DRE and mpMRI findings. (Expert Opinion)
28. In patients with atypical small acinar proliferation (ASAP), clinicians should perform additional testing. (Expert Opinion)
29. In patients with atypical intraductal proliferation (AIP), clinicians should perform additional testing. (Expert Opinion)
30. In patients undergoing repeat biopsy with no prior prostate MRI, clinicians should obtain a prostate MRI prior to biopsy. (Strong Recommendation; Evidence Level: Grade C)
31. In patients with indications for a repeat biopsy who do not have a suspicious lesion on MRI, clinicians may proceed with a systematic biopsy. (Conditional Recommendation; Evidence Level: Grade B)
32. In patients undergoing repeat biopsy and who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy. (Moderate Recommendation [targeted biopsies]/Conditional Recommendation [systematic template biopsy]; Evidence Level: Grade C)

Biopsy Technique

33. Clinicians may use software registration of MRI and ultrasound images during fusion biopsy, when available. (Expert Opinion)
34. Clinicians should obtain at least two needle biopsy cores per target in patients with suspicious prostate lesion(s) on MRI. (Moderate Recommendation; Evidence Level: Grade C)
35. Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C)

INTRODUCTION

Purpose

Prostate cancer is the most commonly diagnosed noncutaneous malignancy in American men. It is estimated that 288,300 patients will be diagnosed with prostate cancer and 34,700 deaths from prostate cancer in the United States (U.S.) in 2023, and an estimated 1,276,106 new cases and 358,989 deaths worldwide reported in 2018.^{1, 2} Significant advances have been made in early detection, especially with the increasing availability and usage of biomarkers as well as mpMRI. This guideline addresses early detection with an emphasis on PSA-based screening, considerations for initial and repeat biopsy, and biopsy technique based on a systematic review of the recently published literature, with the goal of identifying clinically significant prostate cancer.

Terminology and Definitions

This guideline provides recommendations for prostate cancer screening in different groups based on their age range and risk criteria, with an emphasis on SDM. SDM is particularly necessary as there is no universally accepted standard definition of low versus elevated risk for prostate cancer detection. In practice, clinicians often resort to an elevated PSA level based on laboratory, prostate size, or age-based “norms” as a surrogate for an elevated prostate cancer risk, but such definitions, while easy to apply, do not suffice for all people and circumstances. Thus, clinicians may tailor the definitions of elevated risk and elevated PSA to the clinical situation at hand. Some examples that may elevate risk of clinically significant prostate cancer are Black ancestry, germline mutations, strong family history of prostate cancer, and other factors that may be indicated by risk calculators (e.g., total PSA, PSA density, percent free PSA, age). More importantly, this guideline emphasizes potential benefit in using validated risk calculators and provides recommendations for the timing and methodology for screening.

This guideline underscores the goal of detecting “clinically significant” cancer for initial and repeat biopsy. The risk of mortality in patients with GG1 prostate cancer is extremely low.^{3, 4} Thus, this guideline defines clinically significant prostate cancer as GG2 or higher (GG2+) prostate cancer and will use “clinically significant prostate cancer” and “GG2+” interchangeably throughout. However, the Panel acknowledges there are various definitions of “clinically significant” as not all “clinically significant” cancers are destined to impact quality or quantity of life, and it is patient-specific. The guideline recommends utilizing validated risk calculators, particularly calculators that incorporate previous negative biopsy and mpMRI use in the repeat biopsy setting. It also addresses the significance of non-cancerous, yet potentially significant, pathologic findings identified from the biopsy. With the emergence of mpMRI and novel biomarkers, the Panel evaluated the current evidence to develop recommendations on how best to incorporate these into clinical practice. In certain clinical scenarios, additional data are needed to make definitive recommendations for the optimal biopsy approach. An abnormal MRI, for the purpose of this guideline, is defined as PI-RADS 3 to 5 as supported by much of the literature. However, given the local variation and expertise in reading MRIs, some clinicians may opt to limit an abnormal MRI to PI-RADS 4 to 5.

This guideline is intended for all patient populations with a prostate gland. For consistency purposes, this guideline refers to these individuals as “people” or “patients” throughout this document.

Methodology

The systematic review utilized to inform this guideline was conducted by an independent methodological consultant. Determination of the guideline scope and review of the final systematic review to inform guideline statements was conducted in conjunction with the Early Detection of Prostate Cancer Panel.

Panel Formation

The Panel was created in 2021 by the American Urological Association Education and Research, Inc. (AUAER). The Practice Guidelines Committee (PGC) of the AUA selected the Panel Chairs who in turn appointed the additional panel members with specific expertise in this area. The multidisciplinary panel includes representation from urology/urologic oncology, epidemiology, biostatistics, primary care, pathology, and radiology. The Panel additionally included patient representation. Funding of the Panel was provided by the AUA; panel members received no remuneration for their work.

Searches and Article Selection

A search was conducted for existing systematic reviews on October 11, 2021 and updated on November 21, 2022. Systematic reviews published as a component of practice guidelines were also considered eligible for inclusion. An electronic search employing Ovid was used to systematically search the MEDLINE and Embase databases, as well as the Cochrane Library, for systematic reviews evaluating detection of prostate cancer.

When systematic reviews were not identified, or when identified reviews were incomplete, Ovid was used to systematically search MEDLINE and Embase databases for articles evaluating detection of prostate cancer utilizing the PICO elements. During PICO development, panel members submitted landmark studies addressing the Key Questions to the methodologist. These studies were defined as control articles and were compared with the literature search strategy output; the strategy was subsequently updated as necessary to capture all control articles. Databases were originally searched for studies published from January 1, 2000 through October 11, 2021 and subsequently updated to November 21, 2022. In addition to the MEDLINE and Embase database searches, reference lists of included systematic reviews and primary literature were scanned for potentially useful studies.  

All hits from the Ovid literature search were input into reference management software (EndNote X7), where duplicate citations were removed. Abstracts were reviewed by the methodologist to determine if each study addressed the Key Questions and met study design inclusion criteria. For all research questions, randomized controlled trials (RCTs), observational studies, modelling studies with theoretical cohorts, and case-control studies were considered for inclusion in the evidence base. For all Key Questions, studies had to enroll at least 30 patients per study arm. Case series, letters, editorials, in vitro studies, studies conducted in animal models, and studies not published in English were excluded from the evidence base a priori. 

Full-text review was conducted on studies that passed the abstract screening phase. Studies were compared to the PICO criteria as outlined below. Ten panel members were paired with the methodologist and completed duplicate full-text study selection of 10% of studies undergoing full-text review. The dual-review trained the methodologist, who then completed full-time review of the remaining studies.

Data Abstraction

Data were extracted from all studies that passed full-text review by the methodologist.

Risk of Bias Assessment

Quality assessment for all retained studies was conducted. Using this method, studies deemed to be of low quality would not be excluded from the systematic review, but would be retained, and their methodological strengths and weaknesses were discussed where relevant. To evaluate the risk of bias within the identified studies, the Assessment of Multiple Systematic Reviews (AMSTAR),⁵ tool was used for systematic reviews, the Cochrane Risk of Bias Tool⁶ was used for randomized studies, a Risk of Bias in Non-Randomized Studies of Intervention (ROBINS-I)⁷ was used for observational studies and modeling studies with theoretical cohorts, and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2)⁸ was used for diagnostic accuracy studies. Additional important quality features, such as comparison type, power of statistical analysis, and sources of funding were extracted for each study.

Data Synthesis

Meta-analysis was appropriate for studies informing four Key Questions and six outcomes using RevMan.⁹ For all meta-analyses there was substantial heterogeneity in both the patient populations and the methodologies employed within the studies, making random-effects methods the most appropriate. Odds ratios for detection of clinically significant prostate cancer using MRI-targeted biopsy alone and fusion biopsy plus systematic biopsy were calculated based on raw data reported in studies and pooled using an inverse-variance method. For calculation of the number of avoided biopsies and missed clinically significant prostate cancer using various biomarkers in both biopsy naïve and repeat biopsy populations, prevalence and standard errors were extracted or calculated from reported raw data in studies and pooled using an inverse variance method. Finally, prevalence and standard errors for clinically significant prostate cancer detection using a PI-RADS score of 1 to 2, 3, 4, and 5 were calculated from raw data reported in studies and pooled using an inverse-variance method.⁹ Due to the paucity of data using only PI-RADS version 2.1, pooled studies used version 1.0 through version 2.1.

Determination of Evidence Strength

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE)¹⁰ system was used to determine the aggregate evidence quality for each outcome, or group of related outcomes, informing Key Questions. GRADE defines a body of evidence in relation to how confident guideline developers can be that the estimate of effects as reported by that body of evidence, is correct. Evidence is categorized as high, moderate, low, and very low, and assessment is based on the aggregate risk of bias for the evidence base, plus limitations introduced as a consequence of inconsistency, indirectness, imprecision, and publication bias across the studies.¹¹ Additionally, certainty of evidence can be downgraded if confounding across the studies has resulted in the potential for the evidence base to overestimate the effect. Upgrading of evidence is possible if the body of evidence indicates a large effect or if confounding would suggest either spurious effects or would reduce the demonstrated effect.

The AUA employs a 3-tiered strength of evidence system to underpin evidence-based guideline statements. Table 1 summarizes the GRADE categories, definitions, and how these categories translate to the AUA strength of evidence categories. In short, high certainty by GRADE translates to AUA A-category strength of evidence, moderate to B, and both low and very low to C.

Table 1: Strength of Evidence Definitions

The AUA categorizes body of evidence strength as Grade A (e.g., well-conducted and highly-generalizable RCTs or exceptionally strong observational studies with consistent findings), Grade B (e.g., RCTs with some weaknesses of procedure or generalizability or moderately strong observational studies with consistent findings), or Grade C (e.g., RCTs with serious deficiencies of procedure or generalizability or extremely small sample sizes or observational studies that are inconsistent, have small sample sizes, or have other problems that potentially confound interpretation of data). By definition, Grade A evidence is evidence about which the Panel has a high level of certainty, Grade B evidence is evidence about which the Panel has a moderate level of certainty, and Grade C evidence is evidence about which the Panel has a low level of certainty.¹²

AUA Nomenclature: Linking Statement Type to Evidence Strength

The AUA nomenclature system explicitly links statement type to body of evidence strength, level of certainty, magnitude of benefit or risk/burdens, and the Panel’s judgment regarding the balance between benefits and risks/burdens (Table 2). Strong Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is substantial. Moderate Recommendations are directive statements that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be undertaken because net benefit or net harm is moderate. Conditional Recommendations are non-directive statements used when the evidence indicates that there is no apparent net benefit or harm, or when the balance between benefits and risks/burden is unclear. All three statement types may be supported by any body of evidence strength grade. Body of evidence strength Grade A in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances and future research is unlikely to change confidence. Body of evidence strength Grade B in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances, but better evidence could change confidence. Body of evidence strength Grade C in support of a Strong or Moderate Recommendation indicates that the statement can be applied to most patients in most circumstances, but better evidence is likely to change confidence. Conditional Recommendations also can be supported by any evidence strength. When body of evidence strength is Grade A, the statement indicates that benefits and risks/burdens appear balanced, the best action depends on patient circumstances, and future research is unlikely to change confidence. When body of evidence strength Grade B is used, benefits and risks/burdens appear balanced, the best action also depends on individual patient circumstances and better evidence could change confidence. When body of evidence strength Grade C is used, there is uncertainty regarding the balance between benefits and risks/burdens, alternative strategies may be equally reasonable, and better evidence is likely to change confidence.

Where gaps in the evidence existed, the Panel provides guidance in the form of Clinical Principles or Expert Opinions with consensus achieved using a modified Delphi technique if differences in opinion emerged.¹³ A Clinical Principle is a statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in the medical literature. Expert Opinion refers to a statement, achieved by consensus of the Panel, that is based on members’ clinical training, experience, knowledge, and judgment.

Peer Review and Document Approval

An integral part of the guideline development process at the AUA is external peer review. The AUA conducted a comprehensive peer review process to ensure that the document was reviewed by experts who were knowledgeable in the area of early detection of prostate cancer. In addition to reviewers from the AUA PGC, Science and Quality Council (SQC), and Board of Directors (BOD), the document was reviewed by external content experts. Additionally, a call for reviewers was placed on the AUA website from October 10 to 24 of 2022 to allow any additional interested parties to request a copy of the document for review. The guideline was also sent to the Urology Care Foundation and members of the AUA Patient Advocacy network to open the document further to the patient perspective. The draft guideline document was distributed to 174 peer reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 84 reviewers provided comments, including 69 external reviewers. At the end of the peer review process, a total of 770 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted to the AUA PGC, SQC, and BOD for final approval as well as SUO.

Table 2: AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or Risk/Burden, and Body of Evidence Strength

GUIDELINE STATEMENTS

Clinicians should engage in SDM with people for whom prostate cancer screening would be appropriate and proceed based on a person’s values and preferences. (Clinical Principle)

When screening for prostate cancer, clinicians should use PSA as the first screening test. (Strong Recommendation; Evidence Level: Grade A)

For people with a newly elevated PSA, clinicians should repeat the PSA prior to a secondary biomarker, imaging, or biopsy. (Expert Opinion)

Clinicians may begin prostate cancer screening and offer a baseline PSA test to people between ages 45 to 50 years. (Conditional Recommendation; Evidence Level: Grade B)

Clinicians should offer prostate cancer screening beginning at age 40 to 45 years for people at increased risk of developing prostate cancer based on the following factors: Black ancestry, germline mutations, strong family history of prostate cancer. (Strong Recommendation; Evidence Level: Grade B)

Clinicians should offer regular prostate cancer screening every 2 to 4 years to people aged 50 to 69 years. (Strong Recommendation; Evidence Level: Grade A)

Clinicians may personalize the re-screening interval, or decide to discontinue screening, based on patient preference, age, PSA, prostate cancer risk, life expectancy, and general health following SDM. (Conditional Recommendation; Evidence Level: Grade B)

Clinicians may use DRE alongside PSA to establish risk of clinically significant prostate cancer. (Conditional Recommendation; Evidence Level: Grade C)

For people undergoing prostate cancer screening, clinicians should not use PSA velocity as the sole indication for a secondary biomarker, imaging, or biopsy. (Strong Recommendation; Evidence Level: Grade B)

Clinicians and patients may use validated risk calculators to inform the SDM process regarding prostate biopsy. (Conditional Recommendation; Evidence Level: Grade B)

When the risk of clinically significant prostate cancer is sufficiently low based on available clinical, laboratory, and imaging data, clinicians and patients may forgo near-term prostate biopsy. (Clinical Principle)

Clinicians should inform patients undergoing a prostate biopsy that there is a risk of identifying a cancer, with a sufficiently low risk of mortality, that could safely be monitored with AS rather than treated. (Clinical Principle)

Clinicians may use MRI prior to initial biopsy to increase the detection of GG2+ prostate cancer. (Conditional Recommendation; Evidence Level: Grade B)

Radiologists should utilize PI-RADS in the reporting of mpMRI imaging. (Moderate Recommendation; Evidence Level: Grade C)

For biopsy-naïve patients who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy. (Moderate Recommendation [targeted biopsies]/Conditional Recommendation [systematic template biopsy]; Evidence Level: Grade C)

For patients with both an absence of suspicious findings on MRI and an elevated risk for GG2+ prostate cancer, clinicians should proceed with a systematic biopsy. (Moderate Recommendation; Evidence Level: Grade C)

Clinicians may use adjunctive urine or serum markers when further risk stratification would influence the decision regarding whether to proceed with biopsy. (Conditional Recommendation; Evidence Level: Grade C)

For patients with a PSA > 50 ng/mL and no clinical concerns for infection or other cause for increased PSA (e.g., recent prostate instrumentation), clinicians may omit a prostate biopsy in cases where biopsy poses significant risk or where the need for prostate cancer treatment is urgent (e.g., impending spinal cord compression). (Expert Opinion)

Clinicians should communicate with patients following biopsy to review biopsy results, reassess risk of undetected or future development of GG2+ disease, and mutually decide whether to discontinue screening, continue screening, or perform adjunctive testing for early reassessment of risk. (Clinical Principle)

Clinicians should not discontinue prostate cancer screening based solely on a negative prostate biopsy. (Strong Recommendation; Evidence Level: Grade C)

After a negative biopsy, clinicians should not solely use a PSA threshold to decide whether to repeat the biopsy. (Strong Recommendation; Evidence Level: Grade B)

If the clinician and patient decide to continue screening after a negative biopsy, clinicians should re-evaluate the patient within the normal screening interval (two to four years) or sooner, depending on risk of clinically significant prostate cancer and life expectancy. (Clinical Principle)

At the time of re-evaluation after negative biopsy, clinicians should use a risk assessment tool that incorporates the protective effect of prior negative biopsy. (Strong Recommendation; Evidence Level: Grade B)

After a negative initial biopsy in patients with low probability for harboring GG2+ prostate cancer, clinicians should not reflexively perform biomarker testing. (Clinical Principle)

After a negative biopsy, clinicians may use blood, urine, or tissue-based biomarkers selectively for further risk stratification if results are likely to influence the decision regarding repeat biopsy or otherwise substantively change the patient’s management. (Conditional Recommendation; Evidence Level: Grade C)

In patients with focal (one core) HGPIN on biopsy, clinicians should not perform immediate repeat biopsy. (Moderate Recommendation; Evidence Level: Grade C)

In patients with multifocal HGPIN, clinicians may proceed with additional risk evaluation, guided by PSA/DRE and mpMRI findings. (Expert Opinion)

In patients with ASAP, clinicians should perform additional testing. (Expert Opinion)

In patients with AIP, clinicians should perform additional testing. (Expert Opinion)

In patients undergoing repeat biopsy with no prior prostate MRI, clinicians should obtain a prostate MRI prior to biopsy. (Strong Recommendation; Evidence Level: Grade C)

In patients with indications for a repeat biopsy who do not have a suspicious lesion on MRI, clinicians may proceed with a systematic biopsy. (Conditional Recommendation; Evidence Level: Grade B)

In patients undergoing repeat biopsy and who have a suspicious lesion on MRI, clinicians should perform targeted biopsies of the suspicious lesion and may also perform a systematic template biopsy. (Moderate Recommendation [targeted biopsies]/Conditional Recommendation [systematic template biopsy]; Evidence Level: Grade C)

Clinicians may use software registration of MRI and ultrasound images during fusion biopsy, when available. (Expert Opinion)

Clinicians should obtain at least two needle biopsy cores per target in patients with suspicious prostate lesion(s) on MRI. (Moderate Recommendation; Evidence Level: Grade C)

Clinicians may use either a transrectal or transperineal biopsy route when performing a biopsy. (Conditional Recommendation; Evidence Level: Grade C)

FUTURE DIRECTIONS

Screening and diagnosis of prostate cancer remain intensely debated topics with major implications for individual and population health. There continue to be many unanswered questions that can prompt future research, preferably in the form of clinical trials and modeling studies to enhance and optimize patient care. Future trials will hopefully prioritize inclusion of historically underrepresented populations.

SDM regarding whether to screen, how frequently, and when to proceed to secondary testing (e.g., imaging or biomarkers) or biopsy is critically important. However, clinicians tend to discuss potential benefits of screening far more frequently than potential harms.²⁸³ There is an unmet need for decision aids in multiple languages for persons at various levels of health literacy which clearly and comprehensively inform the patient of potential benefits and harms.

For populations at higher risk of being diagnosed with prostate cancer, such as those with a concerning family history of prostate cancer, Black ancestry, genetic risk, or elevated baseline PSA, a targeted and perhaps more intensive screening warrants further investigation. Additionally, investigation of novel approaches is strongly encouraged which may have operating characteristics which outperform currently available tools. Conversely, to minimize overdetection rates, people with a very low likelihood of clinically significant prostate cancer may benefit from less intensive or discontinuation of screening.

Although emerging data exist, a far more comprehensive understanding is required of the impact of race and ethnicity on the operating characteristics of PSA, secondary biomarkers, and prostate imaging. It is also essential to recognize many people undergoing screening are of mixed (or unknown) race and ethnicity. Since dramatic disparities exist regarding access and affordability of certain diagnostic or imaging modalities, efforts should be made by clinicians, payors, and health care systems to bridge this gap. 

For non-binary patients or transgender women there is a lack of data on prostate cancer screening preferences, if and when to initiate, the accuracy of biomarkers (e.g., PSA, secondary biomarkers, MRI), potential psychological consequences, impact of gender-affirming hormonal therapy, and priorities regarding management options.²⁸⁴ Considerably more effort and research are required.

While there are a plethora of serum, urine, tissue, and imaging biomarkers to assess the likelihood of high-grade prostate cancer, there is little knowledge on comparative effectiveness, how they may complement or supplement each other, and how various stepwise algorithms perform. Considerable research is required to achieve the goal of a highly effective, practical, scalable, and widely available approach.

Use of transperineal versus transrectal biopsy varies widely by country and within regions of specific countries. While the transperineal approach may lower the risk of infection without compromising diagnostic capabilities, it is unknown whether prophylactic antibiotics provide value while adequate training and resources are required for wider implementation. Multiple randomized trials of transrectal versus transperineal are ongoing and will provide necessary comparative effectiveness data.

MRI imaging of the prostate, while commonly utilized, has not been shown to impact meaningful long-term outcomes such as cancer-specific mortality. Even with growing clinical experience with mpMRI and fusion biopsies, there remain some cases concerning GG2+ cancer where the targeted biopsy either did not detect cancer or only detected GG1 disease. While this may be due to false positive mpMRI reading, it is also possible that the lesion was under-sampled (e.g., small target in a difficult to access location). How best to manage these cases (e.g., repeat MRI, repeat targeted biopsy, in-bore biopsy) and evolving MRI protocols, such as biparametric MRI and use of artificial intelligence, requires further study.

ABBREVIATIONS

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