Hematuria evaluation: Evidence for optimal practice?

Dr. Caruso is a nurse practitioner at the University of Pennsylvania Health System, Philadelphia. Opinions expressed by bloggers are their own, and do not necessarily reflect the views of Urology Times or its parent company, MultiMedia Healthcare.

Hematuria is a major reason for a clinic encounter, and the most efficient way to evaluate the condition is not always straightforward. While hematuria may represent serious genitourinary pathology, the majority of these evaluations will be negative. In this blog post, I will summarize current evidence and guidance for hematuria evaluation as it pertains to clinicians, including advanced practice providers.

The classic workup

Classic evaluation for hematuria consists of x-ray imaging of the urinary tract, endoscopic evaluation, and urine cytology. Careful assessment is required to rule out benign causes and, if ruled out, should prompt a urologic evaluation. The role of the advanced practice provider in the screening and diagnosis of both macroscopic hematuria and asymptomatic microscopic hematuria requires a proper workup, including ordering the diagnostic tests and prompt referral for cystoscopic examination.

Macroscopic vs. asymptomatic microscopic hematuria

Macroscopic hematuria is alarming to the patient. The dramatic presentation generally ensures compliance. Causes of macroscopic hematuria include asymptomatic or symptomatic stone disease, bladder cancer, and renal tumors. Of course, benign causes, such as infection, medical renal disease, menstruation, or recent urologic procedures, should be ruled out (AUA Guideline: Diagnosis, Evaluation and Follow-up of Asymptomatic Microhematuria (AMH) in Adults).

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The obvious issue is asymptomatic microscopic hematuria. Asymptomatic microscopic hematuria is defined as three or greater red blood cells per high-power field on a properly collected urine specimen in the absence of a benign cause. According to the AUA guideline, a positive dipstick reading merits a formal microscopic examination.

As an alternative, urine dipstick has sometimes been obtained (not on the current AUA guideline) and is sometimes used to define asymptomatic microscopic hematuria as three or greater red blood cells on urine dipstick on two or more occasions. Although there is a 90% sensitivity rate, there is lower specificity with a higher false-positive rate, and the efficacy of urine dipstick is controversial (“Campbell-Walsh Urology,” 11^th ed. Philadelphia: Elsevier, pp. 15).

Other considerations

A concurrent nephrologic workup is warranted when medical renal disease is suspected or in patients taking anticoagulants despite the type or level of anticoagulation therapy. This is pertinent, as anticoagulant therapy is indicated for primary and secondary prevention of stroke, venous thromboembolism, and cardiovascular disease, but also associated with high rates of hematuria-related complications (JAMA 2017; 318:1260-71).

Age is a consideration. A cystoscopy is recommended for individuals older than 35 years while providers have the option to perform cystoscopy at their discretion in those under 35.As for those patients who are at high risk for genitourinary tract malignancies-individuals who are past and current smokers, have irritative bladder symptoms, have chemical exposures or chemotherapy or pelvic radiation exposure-a cystoscopy is recommended, regardless of age.

Next: Upper tract evaluation and cytologyUpper tract evaluation and cytology

Computed tomography urography (CTU) is recommended for the upper tract evaluation (evidence strength grade C), according to the AUA guideline, to best evaluate the renal parenchyma and the urothelium of the upper tracts, and can detect approximately 90% of upper tract malignancies (“Campbell-Walsh Urology,” 11^th ed. Philadelphia: Elsevier, pp. 46).

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As an option, according to expert opinion, when relative contraindications exist, magnetic resonance urography (MRU), magnetic resonance imaging with retrograde pyelograms (RPGs), non-contrast CT, or a combination of renal and bladder ultrasound (RBUS) and RPGs provides an alternative. Cystoscopy with bladder cytology is the standard. The use of urine cytology and urine markers is not recommended as part of the routine evaluation for the asymptomatic microscopic hematuria patient and this is a recommendation based on evidence strength grade C; however, these may be useful for persistent asymptomatic microscopic hematuriafollowing a negative workup or in special circumstances.

Issue of persistence

Persistence also requires consideration. Persistence presents a special challenge as this condition may be associated with an enlarged friable prostate, Randall plaques (calcium plaques), or non-obstructing stones. Patients with a history of persistent asymptomatic microhematuria after an initial evaluation who have had two consecutive negative annual urinalyses do not require additional evaluation. For persistent asymptomatic microscopic hematuria after a negative workup, yearly urinalysis is recommended. If persistent or recurrent after initial workup, a repeat evaluation within 3 to 5 years should be considered. A small portion of patients will have disease or non-malignant disease detected on later evaluations. Provider judgment is key for reevaluation.

Risk of malignancy

There is wide variation in the available data in regard to actual risk of malignancy, and also macroscopic hematuria risk versus asymptomatic microscopic hematuria risk. The risk of malignancy in patients who present with macroscopic hematuria is 20.4% compared to 5.2% in those who present with asymptomatic microscopic hematuria (J Urol 2000; 163:524-7; J Urol 2018; 200:973-80).

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In the recent Detect 1 Clinical Trial of observational design, specifically in the macroscopic hematuria cases, 11% were found to have bladder cancer, 1.4% renal cancer, and 0.8% upper tract urothelial cancer (BMC Cancer 2017; 17:767). Bladder cancer is the most common cancer detected in those who undergo an evaluation for asymptomatic microscopic hematuria (approximately 4.8%), versus renal cancer (0.3%) and upper tract urothelial carcinoma (approximately 0.1%) (J Urol 2000; 163:524-7; J Urol 2018; 200:973-80). Findings from 17 screening studies looking at asymptomatic microscopic hematuria revealed an overall urinary tract malignancy rate of approximately 2.6%, while rates in individual studies ranged from 0% to 25.8% inclusive of repeat testing of high-risk individuals (AUA guideline).

Next: Condensation of thoughtCondensation of thought 

The contemporary AUA guideline provides the basis for rationale care. This includes recommendations (evidence strength grade C),expert opinions, and clinical principles as well as guideline statements.It is essential to understand the nomenclature to be able to critically evaluate the guideline. The most effective approach for a particular patient is best determined by the provider and the patient. However, there is still room for further refinement, which may be provided by patient selection and newer technologies.

Economic consideration 

Balance expense (resource consumption) against inconvenience for patients. There is a high prevalence of asymptomatic microscopic hematuria with a low yield of underlying pathology. Economic consideration should also be regarded in the decision-making process.

In an original investigation, Halpern et al used a decision-analytic, model-based cost-effectiveness analysis to estimate the cost-effectiveness, costs, and incremental cost per cancer detected for four common diagnostic approaches for the evaluation of asymptomatic microscopic hematuria.Using a probabilistic sensitivity analysis, the combination of renal ultrasound and cystoscopy was found to be the most cost-effective, and the use of renal ultrasound in place of CTU as the first-line diagnostic strategy optimized cancer detection and reduced cost of evaluation (JAMA Intern Med 2017; 177:800-7).

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There is the cost of imaging, cystoscopy, provider visits, and time away from work to consider. One might consider individualizing care, but the current guideline does not allow for evidence-based risk stratification. Additionally, there are many patients with asymptomatic persistent microscopic hematuria after a negative workup. Future directions include urine markers and novel imaging. Does hematuria screening affect outcomes? There are few studies available.

Conclusion

CTU, MRU and IV urogram, and RPGs are the recommended modalities to assess the renal parenchyma and upper tracts due to their high sensitivity and specificity. This imaging complements the findings on cystoscopic examination, and there is value in examining the upper tracts. But a new investigation suggests that RBUS in conjunction with cystoscopy can safely replace CTU in patients who have asymptomatic microscopic hematuria. The study suggests that the use of something other than CTU may be worth evaluating further for this group of patients.

Conversely, CTU would remain the recommendation for those patients with macroscopic hematuria due to inferior sensitivity and negative predictive value of RBUS for UTUC (incidence of 0.8%) and renal cancer, as well as renal calculi J Urol 2018; 200:973-80). Non-contrast CT would remain the preferred modality for those with suspected renal calculi.

However, the question remains: Should we consider a risk-stratified approach? Or more importantly, and within these certain parameters and certain settings, can other/alternate modalities safely supplant these traditional modalities?

As always, please feel free to share your perspective by emailing me at UT@advanstar.com.