Sponsoring Organization: American Urological Association (AUA)
| Summary |
> Background A 2012 AUA guideline recommended that all patients older than 35 years with microscopic hematuria undergo computed tomography (CT) urography plus cystoscopy. Now, the AUA is presenting a more nuanced approach, based on both new evidence and recognition that the previous approach subjected many low-risk patients to unnecessary testing . > Key points
> Comment Many of the above recommendations are based on low-level evidence. However, a move away from the previous “one size fits all” approach (with CT urography and cystoscopy fits all), and an emphasis on patient preferences when clinical uncertainty is considerable, are appropriate developments. |
> Prevalence
Hematuria remains one of the most common urologic diagnoses, estimated to account for more than 20% of urologic evaluations. In fact, screening studies have observed a prevalence range of microhematuria (MH) among healthy volunteers of 2.4%-31.1% depending on the specific population screened.
> Etiologies
Urologic etiologies for hematuria include malignancy, infection, inflammation, stone disease, benign prostatic hyperplasia (BPH), and congenital or acquired anatomical anomalies.
Hematuria can also be confused with gynecological sources of bleeding, myoglobinuria, or urine pigmentation from the ingestion of certain foods and medications.
When considering the risk of malignancy in patients with hematuria, a recent prospective observational study of more than 3,500 patients referred for evaluation of hematuria observed a 10.0% rate of urinary tract cancer : 13.2% for patients with gross hematuria (GH) and 3.1 % among patients with MH.
Similarly, aggregate data from 17 previous MH screening studies published between 1980 and 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 .
Eleven more contemporary studies enrolling patients with MH in the current evidence base dating from 2010 to 2019 reported an aggregate rate of urinary tract malignancy of 1% (range 0.3% to 6.25%), which varied depending on the presence or absence of risk factors for malignancy.
> Diagnostic evaluation of microhematuria
While most experts agree that patients with GH should be evaluated with cystoscopy , upper tract imaging, and urinary cytology, there is significant variability between current guidelines and consensus statements regarding MH, particularly the definition of HM, the evaluation criteria, as well as the appropriate components of the evaluation, including the optimal imaging modality.
The 2012 AUA Guideline recommended computed tomography (CT) urography and cystoscopy in all patients older than 35 years with MH, and were designed largely without consideration of patients’ risk of malignancy. In fact, the main objective of the 2012 Guideline was to minimize the probability of missing a diagnosis of malignancy. Consistent with this intent, a theoretical simulation model determined that this screening would not detect the fewest cancers relative to other existing guidelines.
However, this approach carries a risk to the patient (eg, 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 additional research) and an incremental healthcare cost is approximately twice that of other organizations’ guidelines. In light of the overall low rate of cancers detected among patients with MH, the implications of diagnostic studies must be considered at both the patient and health system levels.
At the same time, practice pattern evaluations have demonstrated significant inconsistencies in the evaluation of patients presenting with hematuria. For example, one study found that less than 50% of patients with hematuria diagnosed in a primary care setting were subsequently referred for urologic evaluation.
Furthermore, in a series of patients with hematuria who had known risk factors for bladder cancer, only 23% received any type of imaging and only 13% underwent cystoscopy. The underutilization of cystoscopy, and the tendency to use only imaging for evaluation, is particularly concerning when considering that the vast majority of cancers diagnosed among people with hematuria are bladder cancers, optimally detected with cystoscopy.
Women with hematuria have been especially prone to delays in evaluation, often because professionals attribute hematuria to a urinary tract infection (UTI) or gynecologic source, resulting in inadequate evaluation and delay in evaluation . cancer diagnosis.
Similarly, studies have found that African American patients are less likely than their Caucasian counterparts to undergo any aspect of hematuria evaluation, including urologic referral, cystoscopy, and imaging.
In turn, despite having a lower incidence of bladder cancer than men, women diagnosed with bladder cancer have a lower 5-year survival than men (73.3% versus 78.2%), which can be attributed to part to the delay in diagnosis that leads to a higher stage of the disease at the time of diagnosis.
Similarly, racial differences in five-year survival and stage at diagnosis of urothelial cancer have also been observed , with evidence demonstrating lower urology referral rates and less use of imaging in women and African Americans. with hematuria compared with men and whites, which may explain some of this variation in disease burden at diagnosis and in survival.
Delays in the 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.
As such, there is a need to develop and disseminate clear guideline recommendations for the evaluation of hematuria that limit the unnecessary risks and costs associated with over-evaluation of patients at low risk for malignancy, while at the same time addressing delays in treatment. diagnosis. of major urologic conditions caused by widespread underscreening and variations in care.
Furthermore, since deciding how aggressively to pursue an etiology for MH involves trade-offs at the individual level (risk of malignancy versus assessment harms), it is necessary for the physician and patient to engage in shared decision making , particularly in situations where the relationship Benefits to harms are uncertain, equivalent, or “preference sensitive” (e.g., they depend on the value that an individual patient may assign to them).
This 2020 AUA Guide for MH was developed with these goals in mind. The goal is to provide an individualized approach to the evaluation of hematuria based on the patient’s risk of harboring urinary tract cancer and consistent with the patient’s values.
In the process, it is recognized that tailoring the intensity of screening to the patient’s risk, rather than recommending intensive screening for each patient regardless of harms and costs, will inevitably introduce the potential for some missed cancers.
However, the proposed approach seeks to optimize the balance of detection and risk at both the patient and health system levels. Additionally, the Panel aims to present a set of actionable recommendations that facilitate standardization in order to minimize unnecessary variations and the risk of undervaluation and late diagnosis of important urological conditions.
The recommendations in this document, based on analysis of the best available evidence, represent a patient-centered approach by maximizing opportunities to diagnose important urologic conditions in a timely manner, while avoiding unnecessary evaluations in low-risk patients.
| recommendations |
> 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; Level of evidence: Grade C).
2. Clinicians should not define microhematuria by positive dipstick tests alone. A positive urine dipstick test (trace of blood or more) should prompt formal microscopic evaluation of the urine. (Strong recommendation; Level of evidence: Grade C).
> Initial evaluation
3. In patients with microhematuria, physicians should perform a history and physical examination to evaluate risk factors for genitourinary malignancy, medical kidney disease, gynecologic and non-malignant genitourinary causes of microhematuria. (Clinical principle).
4. Clinicians should perform the same evaluation of patients with microhematuria taking antiplatelet agents or anticoagulants (regardless of type or level of therapy) as patients not receiving these agents. (Strong recommendation; Level of evidence: Grade C).
5. In patients with findings suggestive of a nonmalignant gynecologic or urinary etiology , clinicians should evaluate patients with physical examination techniques and appropriate testing to identify such etiology. (Clinical principle).
6. In patients diagnosed with gynecologic or nonmalignant genitourinary sources of microhematuria, clinicians should repeat urinalysis after resolution of the gynecologic or nonmalignant genitourinary cause. If microhematuria persists or the etiology cannot be identified, clinicians should perform a 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 after treatment to ensure resolution of hematuria. (Strong recommendation; Level of evidence: Grade C).
8. Clinicians should refer patients with microhematuria for nephrologic evaluation if medical kidney disease is suspected. However, risk-based urological evaluation has yet to be performed. (Clinical principle).
> Risk stratification
9. After initial evaluation, clinicians should classify patients presenting with microhematuria as low, intermediate, or high risk for genitourinary malignancy. (Strong recommendation; Level of evidence: Grade C).
> Evaluation of the urinary tract
• Low risk
10. In low-risk patients with microhematuria, clinicians should engage patients in shared decision making to decide whether to repeat urinalysis within six months or continue with cystoscopy and renal ultrasound. (Moderate recommendation; Level of evidence: Grade C).
• Initially low risk with hematuria on repeat urinalysis
11. Low-risk patients who initially chose not to undergo cystoscopy or upper tract imaging and who have microhematuria on repeat urine testing should be reclassified as intermediate or high risk . In such patients, clinicians should perform cystoscopy and upper tract imaging according to recommendations for these risk strata (Strong Recommendation; Level of Evidence: Grade C).
• Intermediate risk
12. Clinicians should perform cystoscopy and renal ultrasound in patients with microhematuria classified as intermediate risk for malignancy. (Strong recommendation; Level of evidence: Grade C).
• High risk
13. Clinicians should perform cystoscopy and upper tract axial imaging in patients with microhematuria classified as high risk for malignancy . (Strong recommendation; Level of evidence: Grade C).
> Options for upper tract imaging in high-risk patients:
- If there are no contraindications to its use, doctors should perform multiphase CT urography (including imaging of the urothelium). (Moderate recommendation; Level of evidence: Grade C).
- If there are contraindications to multiphase CT urography, doctors can use MR urography. (Moderate recommendation; Level of evidence: Grade C).
- If there are contraindications to multiphasic CT urography and MR urography, physicians can use retrograde pyelography in conjunction with non-contrast axial imaging or renal ultrasound. (Expert opinion).
14. Clinicians should perform white light cystoscopy in patients undergoing bladder evaluation for microhematuria. (Moderate recommendation; Level of evidence: Grade C).
15. In patients with persistent or recurrent microhematuria previously evaluated with renal ultrasound, clinicians may perform additional imaging of the urinary tract. (Conditional recommendation; Level of evidence: Grade C).
16. In patients with microhematuria who have a family history of renal cell carcinoma or a known genetic renal tumor syndrome, clinicians should perform upper tract imaging regardless of risk category. (Expert opinion).
> Urinary markers
17. Clinicians should not use urine cytology or urine-based tumor markers in the initial evaluation of patients with microhematuria. (Strong recommendation; Level of evidence: Grade C).
18. Clinicians may obtain urine cytology for patients with persistent microhematuria after a negative examination who have irritant voiding symptoms or risk factors for carcinoma in situ. (Expert opinion).
> Tracking
19. In patients with a negative evaluation for hematuria, physicians may obtain a repeat urinalysis within 12 months. (Conditional recommendation; Level of evidence: Grade C).
20. For patients with a previous negative hematuria evaluation and subsequent negative urinalysis, clinicians may discontinue further evaluation for microhematuria. (Conditional recommendation; Level of evidence: Grade C).
21. For patients with a previous negative hematuria evaluation who have persistent or recurrent microhematuria at the time of repeat urinalysis, clinicians should participate in shared decision making about the need for further evaluation. (Expert opinion).
22. For patients with a previous negative hematuria evaluation who develop macroscopic hematuria, significant increase in the degree of microhematuria, or new urologic symptoms, clinicians should initiate further evaluation . (Moderate recommendation; Level of evidence: Grade C).
