microscopic hematuria work-up

the Am Urol Assn just released their 2020 recommendations for the diagnosis, evaluation and followup of microhematuria (see hematuria guidelines AUA2020 in dropbox, or go to http://auanet.org/guidelines/microhenaturia ).

Main points:

--microhematuria is  defined as >3 RBCs/hpf (high-power microscope field), not by a positive dipstick: strong recommendation, Grade C evidence level

--there should be the same evaluation for patients on antiplatelet or anticoagulant meds as others (history, PE, risk factors for renal dz, GU malignancy, gyn causes): strong recommendation, Grade C evidence level

--if there is other etiology (gyn, gu sources, or UTI), repeat urinalysis for microhematuria to ensure resolution: strong recommendation, Grade C evidence level

--risk-based urologic evaluation should be performed (the 4414 patients studied for the Hematuria Risk Index found that the low risk group had  0.2% chance of malignancy, intermediate risk group 1.6%, and high-risk group 11.1%, with a validation cohort of 3.5K women finding similar numbers). risk assessment suggested per the guidelines: strong recommendation, Grade C evidence level

    --low risk: all of the following: women<50yo/men<40yo; never smoker or <10 pack-yrs; 3-10 RBCs/hpf, no risk factors for urothelial cancer (irritative lower urinary tract sx; prior pelvic irradiation; prior cyclophosphamide/ifosamide chemotherapy; family history of urothelial cancer or Lynch syndrome; occupational exposure to benzene or aromatic amines (eg rubber, petrochemicals, dyes); chronic indwelling foreign body in urinary tract)

    --intermediate risk: any of the following: women 50-59/men 40-59; 10-30 pack-yrs; 11-25 RBC/hpf; low-risk but no prior eval and 3-10 RBC/hpf on repeated urinalysis; additional risk factors for urothelial cancer

    --high risk: any of: women or men >60yo; >30 pack-yrs smoking; >25 RBC/hpf; history of gross hematuria

--urinary tract evaluation (all moderate recommendation, Grade C evidence levels):

    --low-risk: shared decision-making of repeat urinalysis within 6 months, or getting cystoscopy and renal ultrasound: strong recommendation, Grade C evidence level

        --if repeat urinalysis has microhematuria, should treat as intermediate or high-risk (they are pretty unclear on this, commenting that this is dependent on the degree of microhematuria on the repeat)

    --intermediate-risk: cystoscopy and renal ultrasound

    --high-risk: cystoscopy and imaging: multiphasic CT urography if no contraindications; MR urography if contraindications; retrograde pyelography with non-contrast imaging or renal ultrasound if contraindications to both

    --in patients with persistent microhematuria evaluated by ultrasound, may perform other imaging 

    --in patients with family history of renal cell ca or known genetic renal tumor syndrome, perform upper tract imaging independent of risk category, choice of imaging at clinician's discretion (expert opinion)

--do not use urine cytology or urine-based markers in initial evaluaion (not enough data to support), though may get if persistent microhematuria  with negative workup and patient has irritative voiding symptoms or risk factors for carcinoma in situ

--followup:

    --repeat urinalysis in 12 months if negative workup: conditional recommendation, Grade C evidence level

    --can discontinue further urinalysis if workup negative and negative subsequent urinalysis: conditional recommendation, Grade C evidence level

    --if no prior evaluation and recurrent microhematuria, shared decision-making re: need for further workup (expert opinion)

    --if develop gross hematuria, significant increase in microhematuria, or new urologic symptoms, then further evaluation: moderate recommendation, Grade C evidence level

Commentary:

--this guideline applies only to microscopic hematuria. Gross hematuria has a much higher likelihood for urinary tract cancer (13.2% vs 3.1% for microhematuria). more recent studies have suggested an aggregate urinary tract malignancy rate of 1% for microhematuria, varying from 0.3% to 6.25% depending on the presence of risk factors

    --the rate of benign causes far outweighs cancer: even excluding non-urologic causes (eg, gyn ones in women), stones cause about 5-10%, BPH in men for 5-50%

-- this guideline is a welcome change to me, in terms of decreasing ionizing radiation exposure. the US has had a much more aggressive radiologic approach than other countries, with some increased pick-up of cancers, but significant numbers of radiation-induced cancer (which have high fatality rates), very high cost, more morbidity and many more false positives (see http://gmodestmedblogs.blogspot.com/2019/08/hematuria-workup-too-much-radiation.html ). the prior AUA guidelines (2012) recommended CT urography and cystoscopy  for all >35yo with microhematuria [as a perspective here, more patients with microhematuria are referred for imaging than cystoscopy, though the bleeding is much more likely from a bladder source, suggesting that the most important single investigation should be cystoscopy and not upper tract imaging]

    --and, not surprisingly, women and especially women of color, are less likely to have a urologic evaluation; both of these groups tend to be diagnosed with cancer later than men and have a poorer prognosis/increased mortality (though part of the issue is that women do have more sources for hematuria, including vaginal, as well as higher likelihood of UTIs)

limitations of guidelines:

--almost all of the recommendations have Grade C evidence levels, even the strong recommendations, which means "consider the evidence strength to be of low certainty", and "better evidence is likely to change confidence". 

--the definition of microhematuria is based on microscopy, though many sites are moving to automated devices and these results may not correlate well with microscopy

--the data supporting the risk groups should be validated. there have been several studies done, with somewhat different results. the current definition in these guidelines reflects the gestalt of the group and is not backed up by validated studies, and (they admit) does not include all of the risk factors. one evident issue is that their risk profiling includes smoking (important for bladder cancer), though does not include CKD (which is a risk factor for renal cancers, as well as obesity and hypertension, also not on the list). Or does not include schistosomiasis hematobium, which is an important risk factor for bladder cancer in people coming from countries where this infection is common (eg Africa and Middle East). 

--the is uncertainty about whether to use a single urine sample to diagnose microhematuria or multiple ones, given the intermittent nature of the microhematuria; this guideline is based on a single urinalysis

so, these guidelines have moved to a less radiation-intense approach, with likely fewer radiation-induced cancers or radiation-related adverse effects (as per http://gmodestmedblogs.blogspot.com/2019/08/hematuria-workup-too-much-radiation.html ), but there are still many uncertainties:

--one big unanswered issue is who is the group of patients getting the urinalyses and finding microhematuria? this is not a standard screening test is not recommended by the USPSTF.

    --so, the studies referenced in the guidelines are not from the general population (at least the more recent studies: there were old ones on people in HMOs, or the military). this guideline, therefore, represents a lot of data from and expert opinion based on a skewed population.

    --i have had several patients with "incidental" renal cell carcinomas picked up on abdominal CT done for other reasons. given the poor prognosis of late-stage bladder and renal cancers, should we be doing screening urinalyses more regularly??? or are there groups who should get targetted screening (eg smokers??? or those who had worked with aniline dyes or in the rubber industry? or those working with petrochemicals or just pumping gas with the attendant increased benzene exposure?)  and, how often are the incidental cancer pickups actually important anyway (?do they act the same as cancers picked up because of symptoms/signs?)

--another issue skirted over in the guidelines: should the work-up be repeated in those with persistent microhematuria? if so, when? there is a conditional recommendation for repeating at one year. but we know that microhematuria can be intermittent.  is this conditional recommendation enough??

--as with most society guidelines, much of the recommendations are not evidence-based but are more expert opinion. for example, a study of the evolution of cardiology guidelines in the US and Europe found a minority of specific guidelines were evidence-based and that this did not improve comparing guidelines in 2008 to 2018 (see http://gmodestmedblogs.blogspot.com/2019/04/guidelines-lacking-evidence-based.html )?? what guidelines seem to reveal the most is our lack of clear studies to guide us....

geoff

 

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