Published 2020; Amended 2025

Unabridged version of this Guideline [pdf]
Guideline Amendment Summary [pdf]
Algorithm associated with this Guideline [pdf]

To cite this guideline:
Barocas DA, Lotan Y, Matulewicz RS, Raman JD, Westerman ME, Kirkby E, Pak L, Souter L. Updates to Microhematuria: AUA/SUFU Guideline (2025). J Urol. 0(0). doi: 10.1097/JU.0000000000004490. https://www.auajournals.org/doi/abs/10.1097/JU.0000000000004490

Daniel A. Barocas, MD, MPH;* Stephen Boorjian, MD;* Ronald Alvarez, MD, MBA; Tracy M. Downs, MD; Cary Gross, MD; Blake Hamilton, MD; Kathleen Kobashi, MD; Robert Lipman; Yair Lotan, MD; Casey Ng, MD; Matthew Nielsen, MD, MS; Andrew Peterson, MD; Jay Raman, MD; Rebecca Smith-Bindman, MD * Equal author contribution

Daniel A. Barocas, MD, MPH, FACS; Yair Lotan, MD; Richard S. Matulewicz, MD, MSCI, MS; Jay D. Raman, MD, FACS, FRCS(Glasg); Mary E. Westerman, MD

Staff and Consultants

Lauren J. Pak, MHS, MS; Erin Kirkby, MS; Lesley Souter, PhD

Purpose

The purpose of this guideline is to provide a clinical framework for the diagnosis, evaluation, and follow-up of microhematuria (MH).

Methodology

OVID was used to systematically search MEDLINE and EMBASE databases for articles evaluating hematuria using criteria determined by the expert panel. The initial draft evidence report included evidence published from January 2010 through February 2019. A second search conducted to update the report included studies published up to December 2019. Five systematic reviews and 91 primary literature studies met the study selection criteria and were chosen to form the evidence base. These publications were used to create the majority of the clinical framework. When sufficient evidence existed, the body of evidence for a particular modality was assigned a strength rating of A (high), B (moderate), or C (low); and evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed. Additional information is provided as Clinical Principles and Expert Opinions when insufficient evidence exists. In 2024, this Guideline was reviewed via the AUA update literature review (ULR) process, which identified 82 studies for full-text review that were published between December 2019 and June 7, 2024. Of those 82 studies, 23 met inclusion criteria for qualitative synthesis. The subsequent amendment is based on data released since the initial 2020 publication of this Guideline.

GUIDELINE STATEMENTS

Diagnosis and Definition of Microhematuria

1. Clinicians should define microhematuria as >3 red blood cells per high-power field on microscopic evaluation of a single, properly collected urine specimen. (Strong Recommendation; Evidence Level: Grade C)
2. Clinicians should not define microhematuria by positive dipstick testing alone. A positive urine dipstick test (trace blood or greater) should prompt formal microscopic evaluation of the urine. (Strong Recommendation; Evidence Level: Grade C)

Initial Evaluation

3. In patients with microhematuria, clinicians should perform a history, physical examination including blood pressure measurement, and serum creatinine to assess risk factors for genitourinary malignancy (e.g., detailed smoking history), medical renal disease, gynecologic, and non-malignant genitourinary causes of microhematuria. (Clinical Principle) 
4. Clinicians should perform the same evaluation of patients with microhematuria who are taking antiplatelet agents or anticoagulants (regardless of the type or level of therapy) as patients not on these agents. (Strong Recommendation; Evidence Level: Grade C)
5. In patients with findings suggestive of a gynecologic or non-malignant urologic etiology, clinicians should evaluate the patients with appropriate physical examination techniques and tests to identify such an etiology. (Clinical Principle)
6. In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. If microhematuria persists or the etiology cannot be identified, clinicians should perform risk-based urologic evaluation. (Clinical Principle)
7. In patients with hematuria attributed to a urinary tract infection, clinicians should obtain a urinalysis with microscopic evaluation following treatment to ensure resolution of the hematuria. (Strong Recommendation; Evidence Level: Grade C)
8. Clinicians should refer patients with microhematuria for nephrological evaluation if medical renal disease is suspected. However, risk-based urologic evaluation should still be performed. (Clinical Principle)

Risk Stratification

9. Following initial management, clinicians should categorize patients presenting with microhematuria as low/negligible-, intermediate-, or high-risk for genitourinary malignancy based on the accompanying tables (Tables 3 and 4). (Strong Recommendation; Evidence Level: Grade C)

Risk-Based Evaluation

Low/Negligible-Risk

10. In low/negligible-risk patients with microhematuria, clinicians should obtain repeat urinalysis within six months rather than perform immediate cystoscopy or imaging. (Moderate Recommendation; Evidence Level: Grade C)

Initially Low/Negligible-Risk with Hematuria on Repeat Urinalysis

11. Low/negligible-risk patients with microhematuria on repeat urinalysis should be reclassified as intermediate- or high-risk based on repeat urinalysis. In such patients, clinicians should perform risk-based evaluation in accordance with recommendations for these respective risk strata. (Strong Recommendation; Evidence Level: Grade C)

Intermediate-Risk

12. Clinicians should recommend cystoscopy and renal ultrasound in patients with microhematuria categorized as intermediate risk for malignancy. (Strong Recommendation; Evidence Level: Grade C)
13. In appropriately counseled intermediate-risk patients who want to avoid cystoscopy and accept the risk of forgoing direct visual inspection of the bladder urothelium, clinicians may offer urine cytology or validated urine-based tumor markers (Table 5) to facilitate the decision regarding utility of cystoscopy. Renal and bladder ultrasound should still be performed in these cases. (Conditional Recommendation; Evidence Level: Grade C)
14. For patients with intermediate-risk microhematuria who do not undergo cystoscopy based on urinary marker results, clinicians should obtain a repeat urinalysis within 12 months. Such patients with persistent microhematuria should undergo cystoscopy. (Strong Recommendation; Evidence Level: Grade C) 

High-Risk

15. Clinicians should perform cystoscopy and axial upper tract imaging in patients with microhematuria categorized as high-risk for malignancy. (Strong Recommendation; Evidence Level: Grade C)

Options for Upper Tract Imaging in High-Risk Patients:

16. Clinicians should perform white light cystoscopy in patients undergoing evaluation of the bladder for microhematuria. (Moderate Recommendation; Evidence Level: Grade C)
17. In patients with persistent or recurrent microhematuria previously evaluated with renal ultrasound, clinicians may perform additional imaging of the urinary tract. (Conditional Recommendation; Evidence Level: Grade C)
18. In patients with microhematuria who have a family history of renal cell carcinoma, a known genetic renal tumor syndrome, or a personal or family history of (or suspicious for) Lynch syndrome, clinicians should perform upper tract imaging regardless of risk category. (Expert Opinion)

Urinary Markers

19. Clinicians should not routinely use urine cytology or urine-based tumor markers to decide whether to perform cystoscopy in the initial evaluation of low/negligible- or high-risk patients with microhematuria. (Strong Recommendation; Evidence Level: Grade C)
20. Clinicians should not routinely use cytology or urine-based tumor markers as adjunctive tests in the setting of a normal cystoscopy. (Strong Recommendation; Evidence Level: Grade C)
21. Clinicians may obtain urine cytology for high-risk patients with equivocal findings on cystoscopic evaluation or those with persistent microhematuria and irritative voiding symptoms or risk factors for carcinoma in situ after a negative workup. (Expert Opinion)

Follow-Up

22. In patients with a negative risk-based hematuria evaluation, clinicians should engage in shared decision-making regarding whether to repeat urinalysis in the future. (Strong Recommendation; Evidence Level: Grade C)
23. For patients with a prior negative hematuria evaluation and subsequent negative urinalysis, clinicians may discontinue further evaluation for microhematuria. (Conditional Recommendation; Evidence Level: Grade C)
24. For patients with a prior negative hematuria evaluation who have persistent or recurrent microhematuria at the time of repeat urinalysis, clinicians should engage in shared decision-making regarding the need for additional evaluation. (Expert Opinion)
25. For patients with a prior negative hematuria evaluation who develop gross hematuria, significant increase in degree of microhematuria, or new urologic symptoms, clinicians should initiate further evaluation. (Moderate Recommendation; Evidence Level: Grade C)

Prevalence

Hematuria remains one of the most common urologic diagnoses, estimated to account for over 20% of urology evaluations.¹ Indeed, screening studies have noted a prevalence range of microhematuria (MH) among healthy volunteers of 2.4%-31.1% depending on the specific population evaluated.²

Etiologies

Urologic etiologies for hematuria include malignancy, infection, inflammation, calculus disease, benign prostatic hyperplasia (BPH), and congenital or acquired anatomic abnormalities.³ Hematuria may also be confused with gynecological sources of bleeding, myoglobinuria, or pigmentation of the urine from the ingestion of certain foods and drugs. When considering the risk of malignancy in patients with hematuria, a recent prospective observational study of over 3,500 patients referred for evaluation of hematuria noted a 10.0% rate of urinary tract cancer: 13.2% for patients with gross hematuria (GH) and 3.1% among patients with MH only.⁴ Similarly, aggregate data from 17 prior MH screening studies published between 1980 to 2011 identified in the 2012 AUA Guideline reported a urinary tract malignancy rate of 2.6% (range 0% to 25.8%), the vast majority of which were bladder cancers.² Eleven more contemporary studies enrolling MH patients in the current evidence base dating from 2010 to 2019 reported an aggregate urinary tract malignancy rate of 1% (range 0.3% to 6.25%), which varied according to the presence or absence of risk factors for malignancy.^5-15

Diagnostic Evaluation of Microhematuria

While most experts agree that patients with GH should be evaluated with cystoscopy, upper tract imaging and urinary cytology, significant variability exists across current guidelines and consensus statements regarding MH, particularly the definition of MH, criteria for evaluation, as well as the appropriate components of the evaluation, including the optimal imaging modality.^16,17 The 2012 AUA Guideline recommended computed tomography (CT) urography and cystoscopy in all patients over 35 years of age with MH and were largely crafted without regard to an individual patients’ risk of malignancy. Indeed, the principal goal of the 2012 Guideline was to minimize the likelihood of missing a malignancy diagnosis.² Consistent with this intention, a theoretical simulation model determined that this evaluation would miss detection of the fewest number of cancers relative to other existing guidelines.¹⁶ Nevertheless, this approach has attendant patient risk (e.g., discomfort and risk of infection with cystoscopy, risk of contrast reactions, potential for radiation-induced cancers attributed to CT, detection of false-positive findings leading to further investigation),¹⁶ and an incremental healthcare cost approximately twice that of guidelines from other organizations.^16,18 In light of the overall low rate of cancers detected among patients with MH, the implications of diagnostic studies and intensity of evaluation must be considered both at the patient and health system level.

At the same time, practice-pattern assessments have demonstrated significant inconsistencies in the evaluation of patients presenting with hematuria. For example, a 2008 study found that less than 50% of patients with hematuria diagnosed in a primary care setting were subsequently referred for urologic evaluation.¹⁹ Of concern, contemporary studies implicate even lower evaluation rates of under 10%.²⁰ Moreover, in a series of patients presenting with hematuria who had known risk factors for bladder cancer, only 23% received any type of imaging, and only 13% underwent cystoscopy.⁹ The underuse of cystoscopy, and the tendency to solely use imaging for evaluation, is particularly concerning when one considers that most cancers diagnosed among persons with hematuria are bladder cancers, optimally detected with cystoscopy.^{7,9,12,13-15,21-24}

Women with hematuria have been especially prone to delays in evaluation, often due to practitioners ascribing hematuria to a urinary tract infection (UTI) or gynecologic source, resulting in inadequate evaluation and delay in cancer diagnosis.^19,25 Similarly, studies have found that African American patients are less likely than Caucasian counterparts to undergo any aspect of hematuria evaluation, including urology referral, cystoscopy, and imaging.²⁶ In turn, despite having a lower incidence of bladder cancer than men, women diagnosed with bladder cancer have a lower 5-year survival rate than men (73.3% versus 78.2%), which may be in part attributable to delay in diagnosis leading to higher stage disease at diagnosis.²⁷ Likewise, racial differences in five-year survival and stage at diagnosis for urothelial cancer have also been noted, with evidence demonstrating lower rates of referral to urology and lower use of imaging in women and African Americans with hematuria compared to men and whites, which may explain some of this variation in disease burden at diagnosis and in survival.^26,28,29 Delays in diagnosis of bladder cancer have been suggested to contribute to a 34% increased risk of cancer-specific mortality and a 15% increased risk of all-cause mortality.³⁰

As such, the need exists to develop and disseminate clear guideline recommendations for evaluation of hematuria that limit the unnecessary risks and costs associated with the over-evaluation of patients who are at low risk for malignancy, while at the same time addressing the delays in diagnosis of important urologic conditions caused by widespread under-evaluation and variations in care. Furthermore, since the intensity of MH investigation involves tradeoffs at the individual level (risk of malignancy versus harms of evaluation), it is necessary for the clinician and patient to engage in shared decision-making, particularly in situations where the ratio of benefits to harms is uncertain, equivalent or “preference sensitive” (e.g., dependent on the value that an individual patient may place on them).³¹

The 2020 AUA Guideline for MH was developed to provide an individualized approach to microscopic hematuria evaluation based on the patient’s risk of harboring urinary tract cancer and concordant with the patient’s values. At the time, it was acknowledged that tailoring the intensity of evaluation to patient risk, as opposed to recommending intensive evaluation for every patient could introduce the potential for some missed cancers. Nonetheless, the proposed approach sought to optimize the balance of detection and risk at both the patient and health system level. In addition, the Panel put forth an actionable set of recommendations to facilitate standardization to minimize unnecessary variations and the risk of under-evaluation and delayed diagnosis of important urologic conditions. The revised recommendations herein, based on analysis of the best available evidence, represent further refinement of this patient-centered approach by maximizing the opportunities to diagnose important urologic conditions in a timely fashion, while avoiding unnecessary evaluations in low-risk patients.

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 MH Panel.

Panel Formation

The Panel was created in 2018 by the American Urological Association Education and Research, Inc. (AUAER). This guideline was developed in collaboration with the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU). 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 in conjunction with SUFU. Additionally, the Panel included representation from the American College of Obstetricians and Gynecologists (ACOG) as well as a patient advocate. Funding of the Panel was provided by the AUA; panel members received no remuneration for their work. The Microhematuria Amendment Panel was created in 2024 by the AUA to review new literature and provide updates herein.

Searches and Article Selection

A systematic review was conducted to inform on appropriate diagnosis, evaluation, and follow-up in patients with suspected and confirmed MH. The methodologist, in consultation with the expert panel, developed criteria for inclusion and exclusion of studies based on the Key Questions and the populations, interventions, comparators, and outcomes (PICO) of interest. OVID was used to systematically search MEDLINE and EMBASE databases for articles evaluating hematuria using the criteria determined by the expert panel. For the 2020 guideline, 5 systematic reviews and 91 primary literature studies from January 2010 through December 2019 met the study selection criteria and were chosen to form the evidence base. Based on a low volume of studies identified enrolling solely MH patients, studies that enrolled a combination MH and GH population were included in the evidence base. Studies enrolling the two populations were described separately in text and tables.

Control articles, which were deemed important and relevant by the Panel, were compared with the draft literature search strategy output, and the final strategy was updated as necessary to capture all control articles. In addition to the MEDLINE and EMBASE databases searches, reference lists of 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 21), where duplicate citations were removed. Abstracts were reviewed by the methodologist to determine if the study addressed the Key Questions and if the study met study design inclusion criteria. For all research questions, randomized controlled trials (RCTs), observational studies, and case-control studies were considered for inclusion in the evidence base. Studies had to enroll at least 30 patients per study arm for all Key Questions. Additionally, studies evaluating urinary cytology and urine-based tumor markers (UBTM) were required to enroll at least 100 MH patients and in studies of mixed MH and GH populations, at least 25% were required to be MH. Case series, letters, editorials, in vitro studies, studies conducted in animal models, and studies not published in English were excluded from the evidence base.

Full-text review was conducted on studies that passed the abstract screening phase. Studies were compared to the predetermined PICO as outlined below. Nine 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.

Population

• All adult (≥18 years) patients with suspected or confirmed MH
• Studies enrolling populations of both MH and GH patients were considered for inclusion and were used to support recommendations when a paucity of data in exclusively MH patients was available, with additional restrictions detailed above for cytology and UBTM studies.
  • Studies enrolling solely GH populations were excluded

Interventions

• Hematuria detection by urinalysis (UA) or dipstick
• Complete hematuria work-up components
• Risk factors for malignancy and/or mortality
• Imaging modalities
• Cystoscopy
• Urinary cytology and urine-based tumor markers (UBTMs)
• Patient engagement tools and decision aids
• Follow-up schedules in patients with initial negative hematuria evaluation

Comparators

• Any of the included interventions of interest when defined as the control group and compared to another intervention
  • It was anticipated that most of the identified studies would be single arm

Outcomes

• Critical outcomes
  • Hematuria detection concordance (UA versus dipstick)
  • Diagnostic yield, incorporating prevalence of malignant and/or benign diagnoses
  • Diagnostic test characteristics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false positive rate
  • Risk stratification for urologic malignancy
  • Risk stratification system performance characteristics, including predictive ability, prognostic ability, number needed to screen
  • Rate of adverse events and number needed to harm
• Important outcomes
  • Disease specific survival rates
  • Diagnostic grade/stage of malignancy
  • Prevalence of risk factors in hematuria patients
  • Patient satisfaction
  • Quality of life

The initial draft evidence report included evidence published from January 2010 through February 2019. A second search was conducted to update the report to include studies published up to December 2019.

In 2024, the Microhematuria Guideline was updated through the AUA amendment process in which newly published literature was reviewed and integrated into previously published guidelines. An updated literature search of Ovid MEDLINE and Embase identified 82 studies for full-text review that were published between December 2019 and June 7, 2024.

Data Abstraction

Data were extracted from all studies that passed full-text review by the methodologist. All extracted data were audited by an independent auditor.

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 discussed where relevant. To define an overall study quality rating for each included study, risk of bias as determined by validated study-type specific tools, was paired with additional important quality features. To evaluate the risk of bias within the identified studies, the Assessment of Multiple Systematic Reviews (AMSTAR)³² tool was used for systematic reviews, the Cochrane Risk of Bias Tool³³ was used for randomized studies, and a Risk of Bias in Non-Randomized Studies – of Intervention (ROBINS-I)³⁴ was used for observational studies. Additional important quality features, such as study design, comparison type, power of statistical analysis, and sources of funding were extracted for each study.

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE)³⁵ system was used to determine the aggregate evidence quality for each guideline statement. 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 because of inconsistency, indirectness, imprecision, and publication bias across the studies.³⁶ 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.

Data Synthesis

One of the main objectives for the guideline is to establish a risk model to stratify patients based on their risk for underlying urologic malignancy. To this end, pooling of data was conducted in three areas using RevMan.³⁷ For studies that reported adjusted odds ratios (without raw data) for risk factors associated with malignancy, the odds ratios were pooled using a random-effects inverse-variance method. For studies that reported raw data on patient factors and their association with malignant diagnosis, unadjusted odds ratios were calculated and pooled using a random-effects Mantel-Haenszel method. Finally, prevalence of both malignant and benign diagnoses in relation to the type of hematuria work-up received by patients were calculated and pooled using a random-effects inverse-variance method. For all other areas, pooling was determined to be inappropriate based on heterogeneity of population, reference standard, or reported outcomes.

Determination of Evidence Strength

The AUA employs a three-tiered strength of evidence system to underpin evidence-based guideline statements. 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)

The AUA categorizes body of evidence strength as Grade A (well-conducted and highly-generalizable 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.³⁸

As with the 2020 AUA guideline, there remains low and very low strength of evidence to support the guideline statements, highlighting the need to strengthen the evidence through focused research questions in the future.

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. A 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. A 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, 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.³⁹ 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 thorough peer review process to ensure that the document was reviewed by experts in the diagnosis, evaluation, and follow-up of MH. 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 SUFU and ACOG as well as external content experts. Additionally, a call for reviewers was placed on the AUA website from December 2-16, 2019, 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 representatives of the Bladder Cancer Advocacy Network (BCAN) 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, 66 reviewers provided comments, including 51 external reviewers. At the end of the peer review process, a total of 443 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 SUFU for final approval.

For the 2025 Amendment, a call for reviewers was placed on the AUA website from September 4-15, 2024, to allow any additional interested parties to request a copy of the document for review. The draft guideline document was distributed to 90 peer reviewers. All peer review comments were blinded and sent to the Panel for review. In total, 27 reviewers provided comments, including 16 external reviewers. At the end of the peer review process, a total of 133 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 SUFU for final approval.

Clinicians should define microhematuria as >3 red blood cells per high-power field on microscopic evaluation of a single, properly collected urine specimen. (Strong Recommendation; Evidence Level: Grade C)

Clinicians should not define microhematuria by positive dipstick testing alone. A positive urine dipstick test (trace blood or greater) should prompt formal microscopic evaluation of the urine. (Strong Recommendation; Evidence Level: Grade C)

In patients with microhematuria, clinicians should perform a history, physical examination including blood pressure measurement, and serum creatinine to assess risk factors for genitourinary malignancy (e.g., detailed smoking history), medical renal disease, gynecologic, and non-malignant genitourinary causes of MH. (Clinical Principle)

Clinicians should perform the same evaluation of patients with microhematuria who are taking antiplatelet agents or anticoagulants (regardless of the type or level of therapy) as patients not on these agents. (Strong Recommendation; Evidence Level: Grade C)

In patients with findings suggestive of a gynecologic or non-malignant urologic etiology, clinicians should evaluate the patients with appropriate physical examination techniques and tests to identify such an etiology. (Clinical Principle)

In patients diagnosed with gynecologic or non-malignant genitourinary sources of microhematuria, clinicians should repeat urinalysis following resolution of the gynecologic or non-malignant genitourinary cause. If microhematuria persists or the etiology cannot be identified, clinicians should perform risk-based urologic evaluation. (Clinical Principle)

In patients with hematuria attributed to a urinary tract infection, clinicians should obtain a urinalysis with microscopic evaluation following treatment to ensure resolution of the hematuria. (Strong Recommendation; Evidence Level: Grade C)

Clinicians should refer patients with microhematuria for nephrological evaluation if medical renal disease is suspected. However, risk-based urologic evaluation should still be performed. (Clinical Principle)

Following initial management, clinicians should categorize patients presenting with microhematuria as low/negligible-, intermediate-, or high-risk for genitourinary malignancy based on the accompanying tables (Tables 3 and 4). (Strong Recommendation; Evidence Level: Grade C)

GUIDELINE STATEMENT 10

In low/negligible-risk patients with microhematuria, clinicians should obtain repeat urinalysis within six months rather than perform immediate cystoscopy or imaging. (Moderate Recommendation; Evidence Level: Grade C)

GUIDELINE STATEMENT 11

Low/negligible-risk patients with microhematuria on repeat urinalysis should be reclassified as intermediate- or high-risk based on repeat urinalysis. In such patients, clinicians should perform risk-based evaluation in accordance with recommendations for these respective risk strata. (Strong Recommendation; Evidence Level: Grade C)

GUIDELINE STATEMENT 12

Clinicians should recommend cystoscopy and renal ultrasound in patients with microhematuria categorized as intermediate risk for malignancy. (Strong Recommendation; Evidence Level: Grade C)

In appropriately counseled intermediate-risk patients who want to avoid cystoscopy and accept the risk of forgoing direct visual inspection of the bladder urothelium, clinicians may offer urine cytology or validated urine-based tumor markers (Table 5) to facilitate the decision regarding utility of cystoscopy. Renal and bladder ultrasound should still be performed in these cases. (Conditional Recommendation; Evidence Level: Grade C) 

For patients with intermediate-risk microhematuria who do not undergo cystoscopy based on urinary marker results, clinicians should obtain a repeat urinalysis within 12 months. Such patients with persistent microhematuria should then undergo cystoscopy. (Strong Recommendation; Evidence Level: Grade C)

Guideline Statement 15

Clinicians should perform cystoscopy and axial upper tract imaging in patients with microhematuria categorized as high-risk for malignancy. (Strong Recommendation; Evidence Level: Grade C)

Options for Upper Tract Imaging in High-Risk Patients:

Clinicians should perform white light cystoscopy in patients undergoing evaluation of the bladder for microhematuria. (Moderate Recommendation; Evidence Level: Grade C)

In patients with persistent or recurrent microhematuria previously evaluated with renal ultrasound, clinicians may perform additional imaging of the urinary tract. (Conditional Recommendation; Evidence Level: Grade C)

In patients with microhematuria who have a family history of renal cell carcinoma, a known genetic renal tumor syndrome, or a personal or family history of (or suspicious for) Lynch syndrome, clinicians should perform upper tract imaging regardless of risk category. (Expert Opinion)

Clinicians should not routinely use urine cytology or urine-based tumor markers to decide whether to perform cystoscopy in the initial evaluation of low/negligible- or high-risk patients with microhematuria. (Strong Recommendation; Evidence Level: Grade C)

Clinicians should not routinely use cytology or urine-based tumor markers as adjunctive tests in the setting of a normal cystoscopy. (Strong Recommendation; Evidence Level: Grade C)

Clinicians may obtain urine cytology for high-risk patients with equivocal findings on cystoscopic evaluation or those with persistent microhematuria and irritative voiding symptoms or risk factors for carcinoma in situ after a negative work up. (Expert Opinion)

In patients with a negative risk-based hematuria evaluation, clinicians should engage in shared decision-making regarding whether to repeat urinalysis in the future. (Strong Recommendation; Evidence Level: Grade C)

For patients with a prior negative hematuria evaluation and subsequent negative urinalysis, clinicians may discontinue further evaluation for microhematuria. (Conditional Recommendation; Evidence Level: Grade C)

For patients with a prior negative hematuria evaluation who have persistent or recurrent microhematuria at the time of repeat urinalysis, clinicians should engage in shared decision-making regarding the need for additional evaluation. (Expert Opinion)

For patients with a prior negative hematuria evaluation who develop gross hematuria, significant increase in degree of microhematuria, or new urologic symptoms, clinicians should initiate further evaluation. (Moderate Recommendation; Evidence Level: Grade C)

While this Guideline update aims to further refine the evaluation and management of patients with MH, the diagnostic approach to MH is challenging due to its high prevalence and concomitant low incidence of clinically significant disease in the adult population. Despite previous long-standing guidelines recommending urologic evaluation for all patients over 35 years old with MH, referral patterns demonstrated that proportionally very few patients undergo a full evaluation. This highlighted the need for a risk-stratified approach to evaluate MH, as provided by the 2020 AUA/SUFU Microhematuria Guideline. This Guideline introduced risk stratification into low-, intermediate-, and high-risk disease, which the Panel has further refined in this amendment. Nevertheless, the Panel recognizes the lack of high-level supporting evidence for many of the Guideline Statements and acknowledges several existing knowledge gaps that represent opportunities for future investigation to meaningfully enhance care. 

Recent validation studies demonstrated the 2020 risk stratification system separated MH patients into clinically meaningful categories justifying the graduated intensity of evaluation. However, both retrospective and prospective studies utilizing the 2020 stratification system still result in most patients being classified as high-risk (>75%). The current guideline removes otherwise lower-risk women over age 60 from the high-risk group and eliminates the immediate evaluation of low-risk patients, which will mitigate evaluation intensity for these groups. However, further refinement of the risk stratification system, particularly the high-risk cohort, is needed for more accurate identification of those at greatest risk of harboring malignancy and those in whom evaluation can be de-escalated or avoided entirely. While this revised Guideline modifies the existing risk stratification, future work could include incorporation of nomograms or machine learning algorithms for more personalized risk assessment and urinary biomarkers.  

The optimal management of MH may be, at its core, a health system and care delivery issue. Urinalysis is often ordered inappropriately for general screening purposes. Order sets and diagnostic protocols in a variety of settings including annual well visits, emergency department, and preoperative clinic often contain urinalysis orders despite a lack of evidence supporting the practice. For example, 62% of general medicine inpatients have a urinalysis ordered despite 84% being asymptomatic.¹⁴⁵ Despite the high prevalence of MH, most patients never undergo evaluation for MH, and most patients evaluated in urologic clinics appear to be high-risk. Whether this is due to existing referral bias (in that low-risk patients are not referred) or a true limitation of the stratification system is unknown. Future work to understand provider referral practices and how these vary by provider type at a system, regional, and national level is needed. Similarly, an improved understanding of actual risk in patients at low/negligible- and intermediate-risk who are frequently under-evaluated would be of value. 

There is a significant need to apply implementation science methodology and principles to better understand the dissemination and uptake of MH guidelines within healthcare systems. In addition, MH evaluation presents an opportune time for discussion regarding modifiable risk factors – namely smoking. Future work may focus on developing a systems-based approach to incorporating smoking/tobacco use cessation support utilizing institutional or other publicly available resources.  

In addition to evaluating practice patterns regarding asymptomatic MH diagnosis and referral, better understanding of how clinicians diagnose and define MH is needed. New methods for performing urine microscopy are needed. For example, new automated instruments based either on flow cytometry or digitized microscopy are increasingly utilized to perform urinalysis. These machines may not correlate directly with traditional urine microscopy; thus, it will be important to determine if the threshold of 3 RBC/HPF used in the Guideline will be an equivalent predictor of risk when these new technologies are used in evaluation.

The current risk stratification focuses primarily on risk factors for urothelial cancer. Smoking, obesity, hypertension, and chronic kidney disease all represent established risk factors for RCC, of which only smoking is represented in the current risk stratification.²⁴ Depending on the goals of evaluation, a different risk stratification may be necessary to improve recommendations regarding upper tract imaging. The potential benefits of reducing exposure to radiation and contrast agents (with attendant risk of renal issues and allergies) and decreasing healthcare cost are substantial;^16,18,86 however, there exists the risk with this approach of missing small renal masses, UTUC, and small stones. Furthermore, opportunities to reduce radiation exposure with lower or reduced dose protocols deserve additional investigation.^84,85 The need remains to determine whether using lower doses of radiation provides similar sensitivity to detect benign and malignant urologic findings, and which, if any, patient populations or risk groups would be particularly suited for such modified protocols. 

The utility of UBTMs in the evaluation of patients with MH is evolving. Urothelial cancers are in contact with the urine, and this fact has been utilized to evaluate the differential expression of proteins, RNA, DNA, and changes in methylation and cells among patients with malignant and benign conditions. Previous guidelines recommended against using UBTMs including cytology for evaluating MH. While data now exist to support consideration in intermediate-risk populations, use of UBTMs and cytology in low- and high-risk groups is not supported at this time as the results should not change recommended evaluation.

The appropriate incorporation of UBTM/cytology in the evaluation of MH is reliant on accurate risk stratification. Effort and education will need to be undertaken to ensure UBTM/cytology is limited to use in appropriate populations per current Guideline recommendations as a tool to reduce the use of cystoscopy during MH evaluation. Similarly, optimizing follow-up in patients with negative marker testing will be valuable. The necessity of such repeated evaluation should be evaluated as well as the optimal timing and should be a key endpoint for designing prospective marker-based trials. 

This revised Guideline includes recent data demonstrating the low risk of diagnosis of a subsequent malignancy among patients with MH who have a negative evaluation, even among those with persistent (stable) MH. While these patients may be discharged from urologic follow-up, dissemination and implementation beyond urologists may be needed to prevent repeated referrals. Many patients with MH will have persistent findings of microscopic blood – likely due to benign causes that may or may not be recognized – and depending on local practice patterns, may be a risk for persistent re-referral for evaluation. Strategies to mitigate this may be needed in the future.  

Thus, additional prospective research is needed to determine when and how patients with persistent or recurrent MH should be re-evaluated and when it is potentially safe to stop repeat evaluations. Further studies are also needed to guide management and follow up of patients who have a presumed false-positive UBTM test, particularly if done inappropriately in low/negligible- or high-risk groups, and additional non-invasive means of evaluating for the presence of bladder cancer.

Overall, the revised Guideline represents an effort to improve the detection of clinically significant disease while reducing the indiscriminate allocation of healthcare resources and subjecting patients to tests with risk and attendant discomfort/anxiety. MH is a highly prevalent condition, impacting a large population whose evaluation is managed by a wide variety of practitioners. The impact of this Guideline on frequency, intensity, yield of evaluation will need to be studied to determine the impact of the updated recommendations on public health and to inform the next Guideline update.

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