Published 2022; Amended 2026

Unabridged version of this Guideline [pdf]

Amendment summary for this Guideline [pdf]

To cite this guideline: Eastham JA, Barocas D, Chu C, et al. Clinically Localized Prostate Cancer: AUA/ASTRO Guideline Amendment (2026). J Urol. 0(0).10.1097/JU.0000000000005060. https://www.auajournals.org/doi/10.1097/JU.0000000000005060

James A. Eastham, MD; Gregory B. Auffenberg, MD, MS; Daniel A. Barocas, MD, MPH; Roger Chou, MD; Tony Crispino; John W. Davis, MD, Scott Eggener, MD; Eric M. Horwitz, MD; Christopher J. Kane, MD; Daniel W. Lin, MD; Sean M. McBride, MD, MPH; Alicia K. Morgans, MD, MPH; Phillip M. Pierorazio, MD; George Rodrigues, MD; William W. Wong, MD; Stephen A. Boorjian, MD

James A. Eastham, MD, FACS; Daniel A. Barocas, MD, MPH, FACS; Carissa E. Chu, MD; Alicia K. Morgans, MD, MPH; George Rodrigues, MD, PhD

Staff and Consultants

Lauren J. Pak, MHS, MS; Erin Kirkby, MS; Sheena Patel, MPH

Purpose

The recommendations discussed herein for the management of clinically localized prostate cancer provide a framework stratified by risk to facilitate care decisions and guide clinicians in the implementation of selected management options.

Methodology

The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (September 2021), Cochrane Central Register of Controlled Trials (August 2021), and Cochrane Database of Systematic Reviews (September 2021). 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 patients with clinically localized prostate cancer, defined as up to clinical stage T3 (by digital rectal examination [DRE]) prostate cancer without nodal or distant metastasis (N0M0) on conventional imaging. In 2024, an updated literature search was conducted in OVID covering the period from July 1, 2021 to December 5, 2024, overlapping with the original search from the 2021 systematic review. The search identified 29 studies for full-text review plus an additional 8 studies reviewing artificial intelligence (AI) as it relates to disease management. The subsequent 2026 amendment is based on data released since the initial 2022 publication of this Guideline.

GUIDELINE STATEMENTS

Risk Assessment

1. Clinicians should use clinical T stage, serum prostate-specific antigen (PSA), Grade Group (Gleason score), and tumor volume on biopsy to risk stratify patients with newly diagnosed prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
2. Clinicians may selectively use tissue-based genomic biomarkers when added risk stratification may alter clinical decision-making. (Expert Opinion)
3. Clinicians should not routinely use tissue-based genomic biomarkers for risk stratification or clinical decision-making. (Moderate Recommendation; Evidence Level: Grade B)
4. Clinicians should perform an assessment of patient and tumor risk factors to guide the decision to offer germline testing that includes mutations known to be associated with aggressive prostate cancer and/or known to have implications for treatment. (Expert Opinion)

Staging

5. Clinicians may use magnetic resonance imaging (MRI) of the prostate in any risk category to determine extent and location of disease in the prostate, guide surveillance biopsies, or plan treatment. (Conditional Recommendation; Evidence Level: Grade B)
6. Clinicians should not routinely perform prostate-specific membrane antigen positron emission tomography (PSMA PET) scan, cross-sectional imaging, or bone scan for nodal or metastatic staging in asymptomatic patients with low- or favorable intermediate-risk prostate cancer. (Expert Opinion)
7. Clinicians should stage unfavorable intermediate- and high-risk localized prostate cancer using either PSMA PET scan or a combination of bone scan and cross-sectional imaging. (Strong Recommendation; Evidence Level: Grade B)
8. In patients with unfavorable intermediate- and high-risk localized prostate cancer who have negative conventional imaging, clinicians may obtain PSMA PET to evaluate for metastases. (Expert Opinion)

Risk-Based Management

9. Clinicians should inform patients that all prostate cancer treatments carry risk. The risks of treatment to patients’ urinary, sexual, and bowel function must be incorporated with the risk posed by the cancer, patient life expectancy, comorbidities, pre-existing medical conditions, and patient preferences to facilitate a shared decision-making (SDM) approach to management. (Clinical Principle)
10. Clinicians should provide an individualized risk estimate of post-treatment prostate cancer recurrence to patients with prostate cancer. (Clinical Principle)
11. For patients with low-risk prostate cancer, clinicians should recommend active surveillance as the preferred management option. (Strong Recommendation; Evidence Level: Grade A)
12. In asymptomatic patients with prostate cancer and limited life expectancy (determined on a patient-specific basis), clinicians should recommend watchful waiting. (Strong Recommendation; Evidence Level: Grade A)
13. For patients with favorable intermediate-risk prostate cancer, clinicians should discuss active surveillance, radiation therapy, and radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A)
14. Clinicians should inform patients with low- and intermediate-risk prostate cancer that whole gland or focal ablation remains investigational without high-quality data comparing ablation outcomes to standard of care therapies such as surgery, radiation therapy, and active surveillance. (Expert Opinion)
15. For patients with unfavorable intermediate- or high-risk prostate cancer and estimated life expectancy greater than 10 years, clinicians should offer a choice between radical prostatectomy or radiation therapy plus androgen deprivation therapy (ADT). (Strong Recommendation; Evidence Level: Grade A)
16. Clinicians should not recommend whole gland or focal ablation for patients with high-risk prostate cancer outside of a clinical trial. (Expert Opinion)
17. Clinicians may recommend palliative ADT alone for patients with high-risk prostate cancer, local symptoms, and limited life expectancy. (Expert Opinion)

Principles of Management

Principles of Active Surveillance

18. Patients managed with active surveillance should be monitored with serial PSA values and repeat prostate biopsy. (Expert Opinion)
19. In patients selecting active surveillance, clinicians should utilize MRI to augment risk stratification, but this should not replace periodic surveillance biopsy. (Expert Opinion)

Principles of Surgery

20. In patients electing radical prostatectomy, nerve-sparing, when oncologically appropriate, should be performed. (Moderate Recommendation; Evidence Level: Grade B)
21. Clinicians should inform patients that pelvic lymphadenectomy provides staging information, which may guide future management, but does not have consistently documented improvement in metastasis-free, cancer-specific, or overall survival (OS). (Moderate Recommendation; Evidence Level: Grade B)
22. Clinicians should use nomograms to select patients for lymphadenectomy. The potential benefit of identifying lymph node positive disease should be balanced with the risk of complications. (Clinical Principle)
23. Clinicians performing pelvic lymphadenectomy should perform an extended dissection, which improves staging accuracy compared to a limited dissection. (Moderate Recommendation; Evidence Level: Grade: B)
24. Clinicians should complete a radical prostatectomy if suspicious regional nodes are encountered intraoperatively. (Moderate Recommendation; Evidence Level: Grade C)
25. Clinicians should risk stratify patients with positive lymph nodes identified at radical prostatectomy based on pathologic variables and postoperative PSA. (Expert Opinion)
26. Clinicians may offer patients with positive lymph nodes identified at radical prostatectomy and an undetectable post-operative PSA adjuvant therapy or observation. (Conditional Recommendation; Evidence Level: Grade C)
27. Clinicians should not routinely recommend adjuvant radiation therapy after radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A)

Principles of Radiation

28. Clinicians should utilize available target localization, normal tissue avoidance, simulation, advanced treatment planning/delivery, and image-guidance procedures to optimize the therapeutic ratio of external beam radiation therapy (EBRT) delivered for prostate cancer. (Clinical Principle)
29. Clinicians should utilize dose escalation when EBRT is the primary treatment for patients with prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
30. Clinicians may counsel patients with prostate cancer that proton therapy is a treatment option, but it has not been shown to be superior to other radiation modalities in terms of toxicity profile and cancer outcomes. (Conditional Recommendation; Evidence Level: Grade C)
31. Clinicians should offer moderate hypofractionated EBRT for patients with low- or intermediate-risk prostate cancer who elect EBRT. (Strong Recommendation; Evidence Level: Grade A)
32. Clinicians may offer ultra hypofractionated EBRT for patients with low- or intermediate- risk prostate cancer who elect EBRT. (Conditional Recommendation; Evidence Level: Grade B)
33. In patients with low- or favorable intermediate-risk prostate cancer electing radiation therapy, clinicians should offer dose-escalated hypofractionated EBRT (moderate or ultra), permanent low-dose rate (LDR) seed implant, or temporary high-dose rate (HDR) prostate implant as equivalent forms of treatment. (Strong Recommendation; Evidence Level: Grade B)
34. In patients with low- or intermediate-risk prostate cancer electing radiation therapy, clinicians should not electively radiate pelvic lymph nodes. (Strong Recommendation; Evidence Level: Grade B)
35. In patients with low- or favorable intermediate-risk prostate cancer electing radiation therapy, clinicians should not routinely use ADT. (Moderate Recommendation; Evidence Level: Grade B)
36. In patients with unfavorable intermediate-risk prostate cancer electing radiation therapy, clinicians should offer the addition of short-course (four to six months) ADT with radiation therapy. (Strong Recommendation; Evidence Level: Grade A)
37. Clinicians should offer moderate hypofractionated EBRT for patients with high-risk prostate cancer who are candidates for EBRT. (Moderate Recommendation; Evidence Level: Grade C)
38. In patients with unfavorable intermediate- or high-risk prostate cancer electing radiation therapy, clinicians should offer dose-escalated hypofractionated EBRT or combined EBRT + brachytherapy (LDR, HDR) along with a risk-appropriate course of ADT. (Strong Recommendation; Evidence Level: Grade A/B)
39. In patients with high-risk prostate cancer electing radiation therapy, clinicians may offer radiation to the pelvic lymph nodes. (Conditional Recommendation; Evidence Level: Grade B)
40. When treating the pelvic lymph nodes with radiation, clinicians should utilize intensity-modulated radiation therapy (IMRT) with doses between 45 Gy to 52 Gy. (Strong Recommendation; Evidence Level: Grade B)
41. In patients with high-risk prostate cancer electing radiation therapy, clinicians should recommend the addition of long-course (18 to 36 months) ADT with radiation therapy. (Strong Recommendation; Evidence Level: Grade A)
42. When combined ADT and radiation are used, ADT may be initiated neoadjuvantly or concurrently. (Conditional Recommendation; Evidence Level: Grade C)
43. When combining ADT with radiation therapy, clinicians may use combined androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist with an antiandrogen), an LHRH agonist alone, or an LHRH antagonist alone. (Expert Opinion)
44. When treating a subgroup of high-risk localized patients (≥ 2 of the following: PSA ≥ 40 ng/dL, ≥ Gleason 8, ≥ cT3) or locally advanced prostate cancer (cN1) with radiation therapy, clinicians should combine ADT with abiraterone acetate and prednisone for 24 months. (Strong Recommendation; Evidence Level: Grade B)

Follow-up after Treatment

45. Clinicians should monitor patients with prostate cancer post therapy with PSA and symptom assessment. (Clinical Principle)
46. Clinicians should support patients with prostate cancer through continued symptom management and encouraging engagement with professional or community-based resources. (Clinical Principle)

Methodology

The Localized Prostate Cancer Guideline Panel was created in 2019 by the American Urological Association (AUA). This guideline was developed in collaboration with the American Society for Radiation Oncology (ASTRO) with additional representation from the American Society of Clinical Oncology (ASCO) and Society of Urologic Oncology (SUO). The Practice Guidelines Committee (PGC) of the AUA selected the Panel Chair and Vice Chair who in turn appointed the additional panel members with specific expertise in this area in conjunction with ASTRO, ASCO, and SUO. Additionally, the Panel included patient representation. Funding of the Panel was provided by AUA and ASTRO; panel members received no remuneration for their work.

Primary methodology was provided by the Pacific Northwest Evidence-based Practice Center of Oregon Health & Science University (OHSU).¹ The Panel also utilized the systematic review developed by the Agency for Healthcare Research and Quality (AHRQ) on Therapies for Clinically Localized Prostate Cancer.^{2, 3}

The Localized Prostate Cancer Amendment Panel was created in 2024 by the AUA to review new literature and provide updates herein. For this iteration, the systematic review was conducted by an independent methodological consultant, and determination of the guideline scope and review of the final systematic review to inform guideline statements was conducted in conjunction with the Panel.

Data Sources and Searches

A research librarian conducted searches in Ovid MEDLINE (September 2021), Cochrane Central Register of Controlled Trials (August 2021), and Cochrane Database of Systematic Reviews (September 2021). Searches were supplemented by reviewing reference lists of relevant articles. In 2024, an updated literature search of Ovid MEDLINE identified 29 studies for review that were published between July 2021 and December 5, 2024. Inclusion/exclusion was based on the same PICOTS as the original guideline systematic review. An additional 8 studies were identified reviewing AI as it relates to disease management.

Study Selection

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 patients with clinically localized prostate cancer, defined as up to clinical stage T3 (by DRE) prostate cancer without nodal or distant metastasis (N0M0) on conventional imaging. Studies of patients with low-, intermediate-, or high-risk clinically localized prostate cancer were included.

For evaluation of prognostic factors, OHSU included primary studies and systematic reviews that reported risk estimates and controlled for potential confounders, evaluated patients that did not undergo curative treatment or who underwent radical prostatectomy or radiation therapy, and recruited patients in or after 1990. OHSU restricted inclusion to large (n>1,000) studies, unless no such studies were available. Such sample size criterion was only applied to studies of prognosis. For diagnosis, the methodology team included primary studies and systematic reviews that reported diagnostic accuracy or discrimination (e.g., the area under the receiver operating characteristic curve). For evaluation of treatments/management, OHSU focused on randomized trials; if no randomized trials were available, methodologists also included recent, large cohort studies that evaluated comparisons of interest and controlled for confounders. OHSU excluded uncontrolled studies of treatments, case reports, narrative reviews, and non-English language articles. In-vitro and animal studies were also excluded. Articles must have been published in a peer-reviewed journal.

Using the pre-specified criteria, two investigators independently reviewed titles and abstracts of all citations. OHSU used a two-phase method for screening full-text articles identified during review of titles and abstracts. In the first phase, OHSU reviewed full-text articles to identify relevant systematic reviews for inclusion. When there were many primary studies or the primary studies were primarily observational, OHSU utilized systematic reviews that addressed Key Questions, were higher quality, and published within the last five years. The second phase reviewed full-text articles to identify primary studies for key questions not sufficiently answered by previously published systematic reviews, and new studies published after the systematic reviews.

Data Abstraction

For primary studies that met inclusion criteria, a single investigator abstracted information on study design, year, setting, country, sample size, eligibility criteria, dose and duration of the intervention, population characteristics (age, race, tumor stage, tumor grade, PSA level, performance status, prostate cancer risk category), results, and source of funding. For systematic reviews, OHSU abstracted characteristics of the included studies (number, design, and sample sizes of included studies, study settings), population characteristics (inclusion and exclusion criteria), interventions, methods, and ratings for the risk of bias of included studies, synthesis methods, and results. For survival and progression-free survival (PFS), risk estimates were based on the number of deaths or cases of progression, so that estimates <1 indicate improved survival; if necessary, reported risk estimates were converted to this format. Data abstractions were reviewed by a second investigator for accuracy and discrepancies were resolved through discussion and consensus.

Risk of Bias Assessment

Two investigators independently assessed risk of bias using predefined criteria. Disagreements were resolved by consensus. For randomized trials and cohort studies, the methodology team adapted criteria for assessing risk of bias from the U.S. Preventive Services Task Force.⁴ Criteria for randomized trials included use of appropriate randomization and allocation concealment methods, baseline comparability of groups, blinding, attrition, and use of intention-to-treat analysis. For cohort studies on prognostic factors, criteria included methods for assembling cohorts, attrition, blinding assessment of outcomes, and adjustment for potential confounding. OHSU assessed systematic reviews using AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) criteria.⁵ Criteria included use of pre-specified methods, appropriate search methods, assessment of risk of bias, and appropriate synthesis methods. For diagnostic accuracy studies, OHSU adapted criteria from QUADAS-2 to assess risk of bias related to patient selection, interpretation of the index test, selection and interpretation of the reference standard, and flow and timing (e.g., interval between index test and reference standard, receipt of the reference standard, and exclusion of patients from the analysis).⁶ Studies were rated as “low risk of bias,” “medium risk of bias,” or “high risk of bias” based on the presence and seriousness of methodological shortcomings.

Studies rated “low risk of bias” are generally considered valid. “Low risk of bias” randomized trials include clear descriptions of the population, setting, interventions, and comparison groups; a valid method for allocation of patients to treatment; low dropout rates and clear reporting of dropouts; blinding of patients, care providers, and outcome assessors; and appropriate analysis of outcomes.

Studies rated “medium risk of bias” are susceptible to some bias, though not necessarily enough to invalidate the results. These studies do not meet all the criteria for a rating of low risk of bias, but no flaw is likely to cause major bias. Studies may be missing information, making it difficult to assess limitations and potential problems. The “medium risk of bias” category is broad, and studies with this rating vary in their strengths and weaknesses. Therefore, the results of some medium risk of bias studies are likely to be valid, while others may be only possibly valid.

Studies rated “high risk of bias” have significant flaws that may invalidate the results. They have a serious or “fatal” flaw in design, analysis, or reporting; large amounts of missing information; discrepancies in reporting; or serious problems in the delivery of the intervention. The results of high risk of bias studies could be as likely to reflect flaws in study design and conduct as true difference between compared interventions. OHSU did not exclude studies rated high risk of bias a priori, but high risk of bias studies were considered less reliable than low or medium risk of bias studies.

Data Synthesis and Determination of Evidence Strength

OHSU constructed evidence tables with study characteristics, results, and risk of bias ratings for all included studies, and summary tables to highlight the main findings. OHSU reported pooled estimates and other results from systematic reviews and examined whether the findings of new studies were consistent with the reviews.

The AUA employs a three-tiered strength of evidence system to underpin evidence-based guideline statements. (Table 1) The AUA categorizes body of evidence strength as Grade A (well-conducted and highly-generalizable randomized controlled trials [RCTs] or exceptionally strong observational studies with consistent findings), Grade B (RCTs with some weaknesses of procedure or generalizability or moderately strong observational studies with consistent findings), or Grade C (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). 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.⁷

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, when benefits and harms are finely balanced, 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 that 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 that 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 that 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; therefore, 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 of opinion emerged.⁸ 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 for which there may or may not be evidence.

Peer Review and Document Approval

An integral part of the guideline development process at the AUA is external peer review. The AUA conducted a thorough peer review process to ensure that the document was reviewed by experts in the diagnosis and management of Clinically Localized 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 representatives from ASTRO, ASCO, and SUO as well as external content experts. Additionally, a call for reviewers was placed on the AUA website from December 3-17, 2021, 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 representation from prostate cancer patient and advocacy organizations to open the document further to the patient perspective. The draft guideline document was distributed to 115 peer reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 78 reviewers provided comments, including 61 external reviewers. At the end of the peer review process, a total of 668 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted for approval to the AUA PGC, SQC, and BOD as well as the governing body of ASTRO for final approval.

For the 2026 Amendment, a call for reviewers was placed on the AUA website from July 30 – August 15, 2025, to allow any additional interested parties to request a copy of the document for review. The draft guideline document was distributed to 126 peer reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 58 reviewers provided comments, including 50 external reviewers. At the end of the peer review process, a total of 364 comments were received. Following comment discussion, the Panel revised the draft as needed. Once finalized, the guideline was submitted for approval to the original panel and the AUA PGC, SQC, and BOD as well as the governing body of ASTRO for final approval.

Background

Prostate cancer remains the most common non-cutaneous cancer among US men, with an estimated 2,114,850  new cases projected and 626,150 expected deaths in 2026.⁹ As the vast majority of newly-diagnosed prostate cancer patients have clinically localized disease,⁹ providing evidence-based guideline statements to support clinical decision-making represents an important component of facilitating the delivery of standardized, high-quality care.

Given the breadth of investigation into various aspects of the evaluation and management of clinically localized disease that has occurred over the past several years, with the resultant emergence of data relevant to patient care delivery, the AUA, in collaboration with ASTRO, undertook to re-evaluate and update the organization’s prior prostate cancer guidelines.^{10, 11}

An important component of the updated guidelines is the continued utilization of a risk stratification classification for patients with newly diagnosed clinically localized disease. The Panel believes that risk stratification facilitates patient counseling, should be used in SDM for treatment recommendations, and facilitates clinical trial enrollment. Recognizing that various risk classifications have been described,^10-14 the Panel elected to maintain a risk group model (Table 3). Of note, the Panel did combine the prior risk categories of “very low-risk” and “low-risk” disease together, as the recommended management for these patients is consistent. The Panel understands that risk assessment may be refined as new information becomes available. The intention of the risk groups is to provide a framework to discuss management options. The importance of SDM between patient and clinician is emphasized in the statements and supporting text. In addition to detailing the components of risk stratification, the Guideline is also intended to address indications for staging in the newly diagnosed patient, provide risk-based treatment approaches to be reviewed by the clinician with the patient, and offer recommendations for post-treatment follow-up. Further, information is outlined regarding specifics of care delivery for various therapeutic modalities, such as pelvic lymph node management during radical prostatectomy, radiation dosage, fields, and concurrent ADT usage, as well as principles of conducting active surveillance. Further, the Panel identified several areas of ongoing study that are likely to be of significant relevance in the future for the care of patients with clinically localized disease, including genomic tumor tissue testing and advanced imaging.

Clinicians should use clinical T stage, serum PSA, Grade Group (Gleason score), and tumor volume on biopsy to risk stratify patients with newly diagnosed prostate cancer. (Strong Recommendation; Evidence Level: Grade A)

Clinicians may selectively use tissue-based genomic biomarkers when added risk stratification may alter clinical decision-making. (Expert Opinion)

Clinicians should not routinely use tissue-based genomic biomarkers for risk stratification or clinical decision-making. (Moderate Recommendation; Evidence Level: Grade B)

Clinicians should perform an assessment of patient and tumor risk factors to guide the decision to offer germline testing that includes mutations known to be associated with aggressive prostate cancer and/or known to have implications for treatment. (Expert Opinion)

Clinicians may use MRI of the prostate in any risk category to determine extent and location of disease in the prostate, guide surveillance biopsies, or plan treatment. (Conditional Recommendation; Evidence Level: Grade B)

Clinicians should not routinely perform PSMA PET scan, cross-sectional imaging, or bone scan for nodal or metastatic staging in asymptomatic patients with low- or favorable intermediate-risk prostate cancer. (Expert Opinion)

Clinicians should stage unfavorable intermediate- and high-risk localized prostate cancer using either PSMA PET scan or a combination of bone scan and cross-sectional imaging. (Strong Recommendation; Evidence Level: Grade B)

In patients with unfavorable intermediate- and high-risk localized prostate cancer who have negative conventional imaging, clinicians may obtain PSMA PET scan to evaluate for metastases. (Expert Opinion)

Clinicians should inform patients that all prostate cancer treatments carry risk. The risks of treatment to patients’ urinary, sexual, and bowel function must be incorporated with the risk posed by the cancer, patient life expectancy, comorbidities, pre-existing medical conditions, and patient preferences to facilitate a SDM approach to management.  (Clinical Principle)

Clinicians should provide an individualized risk estimate of post-treatment prostate cancer recurrence to patients with prostate cancer. (Clinical Principle)

For patients with low-risk prostate cancer, clinicians should recommend active surveillance as the preferred management option. (Strong Recommendation; Evidence Level: Grade A)

In asymptomatic patients with prostate cancer and limited life expectancy (determined on a patient-specific basis), clinicians should recommend watchful waiting. (Strong Recommendation; Evidence Level: Grade A)

For patients with favorable intermediate-risk prostate cancer, clinicians should discuss active surveillance, radiation therapy, and radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A)

Clinicians should inform patients with low- and intermediate-risk prostate cancer that whole gland or focal ablation remains investigational without high-quality data comparing ablation outcomes to standard of care therapies such as surgery, radiation therapy, and active surveillance. (Expert Opinion)

For patients with unfavorable intermediate- or high-risk prostate cancer and estimated life expectancy greater than 10 years, clinicians should offer a choice between radical prostatectomy or radiation therapy plus ADT. (Strong Recommendation; Evidence Level: Grade A)

Clinicians should not recommend whole gland or focal ablation for patients with high-risk prostate cancer outside of a clinical trial. (Expert Opinion)

Clinicians may recommend palliative ADT alone for patients with high-risk prostate cancer, local symptoms, and limited life expectancy. (Expert Opinion)

Patients managed with active surveillance should be monitored with serial PSA values and repeat prostate biopsy. (Expert Opinion)

In patients selecting active surveillance, clinicians should utilize MRI to augment risk stratification, but this should not replace periodic surveillance biopsy. (Expert Opinion)

In patients electing radical prostatectomy, nerve-sparing, when oncologically appropriate, should be performed. (Moderate Recommendation; Evidence Level: Grade B)

Clinicians should inform patients that pelvic lymphadenectomy provides staging information, which may guide future management, but does not have consistently documented improvement in metastasis-free, cancer-specific, or OS. (Moderate Recommendation; Evidence Level: Grade B)

Clinicians should use nomograms to select patients for lymphadenectomy. The potential benefit of identifying lymph node positive disease should be balanced with the risk of complications. (Clinical Principle)

Clinicians performing pelvic lymphadenectomy should perform an extended dissection, which improves staging accuracy compared to a limited dissection. (Moderate Recommendation; Evidence Level: Grade: B)

Clinicians should complete a radical prostatectomy if suspicious regional nodes are encountered intraoperatively. (Moderate Recommendation; Evidence Level: Grade C)

Clinicians should risk stratify patients with positive lymph nodes identified at radical prostatectomy based on pathologic variables and postoperative PSA. (Expert Opinion)

Clinicians may offer patients with positive lymph nodes identified at radical prostatectomy and an undetectable post-operative PSA adjuvant therapy or observation. (Conditional Recommendation; Evidence Level: Grade C)

Clinicians should not routinely recommend adjuvant radiation therapy after radical prostatectomy. (Strong Recommendation; Evidence Level: Grade A)

Clinicians should utilize available target localization, normal tissue avoidance, simulation, advanced treatment planning/delivery, and image-guidance procedures to optimize the therapeutic ratio of EBRT delivered for prostate cancer. (Clinical Principle)

Clinicians should utilize dose escalation when EBRT is the primary treatment for patients with prostate cancer. (Strong Recommendation; Evidence Level: Grade A)

Clinicians may counsel patients with prostate cancer that proton therapy is a treatment option, but it has not been shown to be superior to other radiation modalities in terms of toxicity profile and cancer outcomes. (Conditional Recommendation; Evidence Level: Grade C)

Clinicians should offer moderate hypofractionated EBRT for patients with low- or intermediate-risk prostate cancer who elect EBRT. (Strong Recommendation; Evidence Level: Grade A)

Clinicians may offer ultra hypofractionated EBRT for patients with low- or intermediate-risk prostate cancer who elect EBRT. (Conditional Recommendation; Evidence Level: Grade B)

In patients with low- or favorable intermediate-risk prostate cancer electing radiation therapy, clinicians should offer dose-escalated hypofractionated EBRT (moderate or ultra), permanent low-dose rate (LDR) seed implant, or temporary high-dose rate (HDR) prostate implant as equivalent forms of treatment. (Strong Recommendation; Evidence Level: Grade B)

In patients with low- or intermediate-risk prostate cancer electing radiation therapy, clinicians should not electively radiate pelvic lymph nodes. (Strong Recommendation; Evidence Level: Grade B)

In patients with low- or favorable intermediate-risk prostate cancer electing radiation therapy, clinicians should not routinely use ADT. (Moderate Recommendation; Evidence Level: Grade B)

In patients with unfavorable intermediate-risk prostate cancer electing radiation therapy, clinicians should offer the addition of short-course (four to six months) ADT with radiation therapy. (Strong Recommendation; Evidence Level: Grade A)

Clinicians should offer moderate hypofractionated EBRT for patients with high-risk prostate cancer who are candidates for EBRT. (Moderate Recommendation; Evidence Level: Grade C)

In patients with unfavorable intermediate- or high-risk prostate cancer electing radiation therapy, clinicians should offer dose-escalated hypofractionated EBRT or combined EBRT + brachytherapy (LDR, HDR) along with a risk-appropriate course of ADT. (Strong Recommendation; Evidence Level: Grade A/B)

In patients with high-risk prostate cancer electing radiation therapy, clinicians may offer radiation to the pelvic lymph nodes. (Conditional Recommendation; Evidence Level: Grade B)

When treating the pelvic lymph nodes with radiation, clinicians should utilize IMRT with doses between 45 Gy to 52 Gy. (Strong Recommendation; Evidence Level: Grade B)

In patients with high-risk prostate cancer electing radiation therapy, clinicians should recommend the addition of long-course (18 to 36 months) ADT with radiation therapy. (Strong Recommendation; Evidence Level: Grade A)

When combined ADT and radiation are used, ADT may be initiated neoadjuvantly or concurrently. (Conditional Recommendation; Evidence Level: Grade C)

When combining ADT with radiation therapy, clinicians may use combined androgen suppression (LHRH agonist with an antiandrogen), an LHRH agonist alone, or an LHRH antagonist alone. (Expert Opinion)

When treating a subgroup of high-risk localized patients (≥ 2 of the following: PSA ≥ 40 ng/dL, ≥ Gleason 8, ≥ cT3) or locally advanced prostate cancer (cN1) with radiation therapy, clinicians should combine ADT with abiraterone acetate and prednisone for 24 months. (Strong Recommendation; Evidence Level: Grade B)

Clinicians should monitor patients with prostate cancer post therapy with PSA and symptom assessment. (Clinical Principle)

Clinicians should support patients with prostate cancer through continued symptom management and encouraging engagement with professional or community-based resources. (Clinical Principle)

Clinically localized prostate cancer remains one of the most active areas of investigation in urology. A few topics of practice-changing study are highlighted here:

Treatment Intensification for High-Risk Disease

Multiple trials evaluating next generation androgen signaling inhibitors in high-risk clinically localized disease have accrued and are awaiting results. In the Apa-RP trial, adjuvant apalutamide for high-risk prostatectomy patients has demonstrated excellent biochemical control.³¹¹ This phase 2 trial showed a 100% biochemical recurrence-free survival at 24 months among 108 high-risk prostate cancer patients who received 12 months of apalutamide combined with ADT following radical prostatectomy. PROTEUS, a randomized, double-blind, placebo-controlled, phase 3 trial of apalutamide plus ADT versus placebo plus ADT prior to radical prostatectomy in patients with localized high-risk or locally advanced prostate cancer has also completed enrollment. PROTEUS aims to improve pathologic complete response rates and MFS. Final outcomes should be available in late 2028. Further, DASL-HiCaP randomized in a 1:1 fashion 1100 patients with planned radiation therapy with very high-risk localized prostate cancer on conventional imaging or very high-risk features with PSA persistence or rise within 12 months of radical prostatectomy. Patients were randomized to receive darolutamide or placebo twice daily for 96 weeks in combination with 96 weeks of ADT plus radiation therapy starting 8-24 weeks from randomization. The primary endpoint is MFS.

Surgical Innovation

Intraoperative imaging for robotic surgery has the potential to improve functional outcomes, margin status, and node dissection. PSMA targeting fluorophores and radioguided surgery enable real-time tumor visualization. Early studies show safety and feasibility. Fluorescence–guided prostatectomy (first-in-human) for margin status and nerve preservation demonstrate early improvements in surgical technique particularly in reoperative or node-positive settings.^{312, 313} Focal therapy in prostate cancer including all modalities such as HIFU, IRE, PDT, and cryoablation are undergoing extensive evaluation in prospective studies. Future practice must balance long-term oncologic outcomes with preserving urinary and sexual function.

Biomarkers

The ability for commercially available GCs to improve the outcomes of patients with clinically localized prostate cancer has not been validated in prospective clinical trials to date. Thus, routine use is not recommended at this time. A specific important limitation of the existing data supporting the prognostic capacity of GCs is that studies have been primarily based on tissue analysis of radical prostatectomy specimens. As such, the impact of tissue heterogeneity and under-sampling on the prognostic ability of GCs for assessing the risks of recurrence, metastasis, and death from prostate cancer biopsies remains uncertain. Of note, accumulating evidence has indicated that GC scores, specifically Decipher, derived from biopsy specimens do correlate with cancer outcomes. For example, Nguyen et al. reported on 235 radical prostatectomy/radiation therapy patients for whom Decipher was run on biopsy specimens and found that, on multivariable analysis, Decipher score was associated with both the risks of metastasis and prostate cancer-specific mortality.³¹⁴ In addition, the prognostic capacity of biopsy-based Decipher was validated using prospectively collected, banked specimens from RTOG 9202, 9413, and 9902. After adjusting for age, PSA, Gleason score, cT-stage, trial and randomized treatment arm, Decipher score was associated with distant metastases, prostate cancer-specific mortality, and OS.³¹⁵

Prospective validation of the predictive capacity of GCs in localized disease will be important to support widespread use for treatment selection. Several ongoing clinical trials (e.g. NRG GU009 and GU 010) are indeed evaluating treatment intensification and de-intensification based on GC (Decipher) results in both intermediate- and high-risk patient populations.

AI for interpretation of hematoxylin and eosin slides will also be practice-changing. Artera AI’s multimodal AI biomarker test applies a deep learning algorithm to digitized biopsy slides developed and validated in large cooperative group trials such as NRG/RTOG 9202, 9408, 9413, 9910, and 0126.³¹⁶ Artera AI not only stratifies risk, but also predicts which patients benefit from adding ADT to radiation, enabling more precise personalization of therapy while reducing overtreatment and toxicity.

Imaging

The PRIME study demonstrated that a two-sequence (bi-parametric) MRI was non-inferior to standard contrast-enhanced mpMRI for detecting clinically significant prostate cancer, which may reduce cost, improve access, and increase screening efficiency. Utilization of bi-parametric MRI is likely to increase diagnosis, improve monitoring during active surveillance, and treatment planning.⁷⁹

High-resolution micro-ultrasonography (microUS) is an alternative to mpMRI for detecting clinically significant prostate cancer.³¹⁷ While MRI is still standard, microUS can be considered when MRI is inconclusive, if the patient is claustrophobic, or the patient has metal implants.

As noted in the updated guideline statements, PSMA PET has greater sensitivity than conventional imaging for identification of nodal and distant disease, and evidence that PSMA PET imaging can substantially alter the treatment plan and expectations regarding outcomes of treatment ⁹¹ (e.g., finding small volume metastatic disease on PSMA PET in a patient otherwise thought to have localized disease by conventional imaging).  PSMA PET is a first-line option for staging in patients with unfavorable intermediate-risk or high-risk prostate cancer.

Several imaging radiotracers utilizing PET-based technology have been demonstrated to improve detection of disease over conventional imaging. Broadly, these imaging modalities have been referred to as next-generation imaging (NGI); among these, PSMA-based PET scanning has received the most attention. This interest has been bolstered by FDA approval of two PSMA-based tracers: Gallium 68 PSMA-11 (Ga 68 PSMA-11) and piflufolastat F-18 (18F-DCFPyL).^{318, 319} Moreover, continued evaluation of novel PSMA PET agents remains ongoing.³²⁰ As such, PSMA PET is an accepted standard in the staging evaluation of patients with localized high-risk prostate cancer. Nevertheless, future studies are needed to determine how the information from NGI should be incorporated into clinical decision-making due to both the limitations of these advanced imaging techniques and the fact that the data to date on outcomes following treatment upon which management recommendations are based on patients evaluated with conventional imaging. For example, in the OSPREY trial in which patients underwent F-18 DCFPyl-PET/CT followed by radical prostatectomy and extended PLND, the sensitivity of the scan for detection of pelvic lymph node disease was only 40.3%, suggesting this study alone could not be used to triage patients as to whether or not to undergo lymph node dissection at the time of surgery.³²¹ At the same time, in 12.3% of high-risk patients, F-18 DCFPyl identified extra-pelvic disease, indicating patients for whom additional therapy would be indicated.³²¹ Prospective studies incorporating NGI as staging will be required to determine clinical utility. Until such data are available, clinicians should exercise caution when using PSMA PET results to justify substantial alterations in standard-of-care treatments the utility of which has been established among patients who were staged with conventional imaging.

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