Asymptomatic Microscopic Hemature : 2012 AUA Guidelines

2012 AUA Guidelines

ASYMPTOMATIC MICROSCOPIC HEMATURIA:

2012 AUA GUIDELINES

Andrew James Tompkins, M.D.Clinical Instructor in Surgery (Urology)The Warren Alpert School of Medicine at Brown UniversityUrologic Specialists of New EnglandAndrew_Tompkins@Brown.edu

I’m not actually 5’11 I don’t usually wear a suitDidn’t get much sleepNothing to disclose

DISCLOSURES

To define asymptomatic microscopic hematuria (AMH).

Identify patients that require urologic referral.

Discuss the ideal evaluation of AMH.

What should I send to the urologist that would be helpful? Focus less on “data” and more on evaluation process.

OBJECTIVES

58 yo female with history of smoking, HTN, DM, and recurrent UTI’s presents for evaluation of urinary frequency.

Urine Dipstick: + 2 Blood, + LE, - Nit, - Protein

Does this patient need a hematuria evaluation?

Lets find out.

CASE

“3 or greater RBC per high power field on a properly collected urinary specimen in the absence of obvious benign cause”

Dipstick is insufficient! Sensitive not specific 35% false positive

Obvious Benign Cause Infection Menstruation* Vigorous exercise Viral illness Trauma Recent urologic procedure

AMH - DEFINED

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012Rao, PK et. al.: Dipstick Pseudohematuria: Unnecessary Consultation and Evaluation. Journal of Urology. 2010. Vol. 183. 560-565

Change from 2001 guideline “2 of 3 urine specimens with 3 or more RBC.”

Indirect evidence supports 1 positive sample Microhematuria caused by malignancy is highly intermittent…

multiple samples may lead to missed diagnosis

Studies show malignancy rate of 3.3% (95% CI 2.2-5%) with one sample. Not significantly different from multiple samples.

Patients “benefit” from active management of frequently diagnosed conditions during AMH evaluation.

AMH - DEFINED

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012

Stone Disease – 6.0% (95% CI 3.8-9.2%)

Benign Prostate Enlargement – 12.9% (95% CI 6.3-24.6%) 30%-40% in my patient population

Urethral Stricture – 1.4% (95% CI 0.6-3.2%)

GU Malignancy - 3.3% (95% CI 2.2-5%)

AMH - DIAGNOSIS

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012

58 yo female with history of smoking, HTN, DM, and recurrent UTI’s presents for evaluation of urinary frequency.

Urine Dipstick - + Blood, + LE, - Nit

Microscopy – 3 RBC, 10 WBC, Urine Culture - > 100,000 E. Coli

Does this patient need a hematuria evaluation?

Repeat UA with Micro in 4 weeks.

CASE CONTINUED

Retrospective chart review of two urologists at Cleveland Clinic between 2006-2008

91 patients met inclusion criteria as referral for AMH 59.3% - referred on + dipstick only 16.5% - referred + dipstick and micro <3rbc 24.2% - referred on + dipstick and micro > 3rbc

57% (52/91) consults had “pseudohematuria” 52% (27/52) – patients deferred evaluation c counseling on

guidelines 48% (25/52) – patients requested evaluation despite urologist

counseling against additional evaluation Cost $26,792 based on 2009 Medicare reimbursements

AMH - REFERRAL

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012Rao, PK et. al.: Dipstick Pseudohematuria: Unnecessary Consultation and Evaluation. Journal of Urology. 2010. Vol. 183. 560-565

25% of inappropriate referrals were found to have

AMH on urology evaluation

AMH - REFERRAL

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012Rao, PK et. al.: Dipstick Pseudohematuria: Unnecessary Consultation and Evaluation. Journal of Urology. 2010. Vol. 183. 560-565

Prevalence

Rate of AMH range from 2.4% to 31% in health screening studies.

Highest rates in Men ≥ 60 yo

Smokers/former smokers.

AMH - BACKGROUND

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012Loo, RK et. al.: Stratifying Risk of Urinary Tract Malignant Tumors in Patients With Asymptomatic Microscopic Hematuria. Mayo Clinic Proceedings. 2013

Male genderAge ≥ 35Past/Current

smokingChemical exposureAnalgesic abuseHx gross hematuriaHx irritive voiding

symptoms

AMH – AUA RISK FACTORS FOR MALIGNANCY

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012

Hx pelvic irradiationHx chronic utiHx of

cyclophosphamide*Chronic indwelling

foreign body

2630 patients referred for AMH in southern California between 2009 & 2011 (prior to 2012 guidelines)

> 3 RBC on 2/3 properly collected specimens

Renal or Bladder Cancer – 1.9% (3.3% on meta-analysis)

RF – Age > 50 yo, hx gross hematuria, male sex.

Hematuria Risk Index Low Risk (32%) – 0.2% risk of cancer High Risk (14%) – 11.1% risk of cancer

AMH – MALIGNANCY RISK

Loo, RK et. al.: Stratifying Risk of Urinary Tract Malignant Tumors in Patients With Asymptomatic Microscopic Hematuria. Mayo Clinic Proceedings. 2013

58 yo female with history of smoking, HTN, DM, and recurrent UTI’s presents for evaluation of urinary frequency.

Microscopy – 3 RBC, 10 WBC, Urine Culture - > 100,000 E. Coli,

Repeat UA with Micro in 4 weeks 3 RBC, 5 WBC Urine Culture - No Growth

Should I refer to urology? Yes!

CASE CONTINUED

Urinalysis & Microscopy – dysmorphic RBC, proteinuria, cellular casts, renal insufficiency → nephrology consult

GFR – (BUN, Cr) → Impaired renal function → nephrology consult

Imaging - CTU

Cystoscopy - All patients ≥ 35 years old & < 35 years old with risk factors

AMH - EVALUATION

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012

Midstream Clean Catch UA dipstick and Microscopy If contaminated – repeat Send UA dipstick and microscopy with referral

Urinalysis – dysmorphic RBC, proteinuria, cellular casts Nephrology consult

Continue Urologic Evaluation

AMH - URINALYSIS

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012

GFR – (BUN, Cr) → Impaired renal function → nephrology consult *Send recent BMP with referral GFR has implications with CTU & MRU

Continue Urologic Evaluation

AMH - GFR

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012

CTU – without, with, & with delayed imaging w/o – stones, backdrop for enhancement W – renal masses, renal artery stenosis, assess for

enhancement Delayed – assess collecting system for filling defects

ASYMPTOMATIC MICROSCOPIC HEMATURIA - IMAGING

Chlapoutakis K, et al: Performance of computed tomographic urography in diagnosis of upper urinary tract urothelial carcinoma, in patients presenting with hematuria: Systematic review and meta-analysis. Eur J Radiol 2010; 73: 334

AMH- IMAGING

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012

58 yo female with history of smoking, HTN, DM, and recurrent UTI’s presents for evaluation of urinary frequency.

Microscopy – 3 RBC, 10 WBC, Urine Culture - > 100,000 E. Coli,

Repeat UA with Micro in 4 weeks 3 RBC, 5 WBC Urine Culture - No Growth Serum Cr 1.7 eGFR 39ml/min/1.73m2

You want to get the ball rolling and order imaging. What imaging test should you order? CTU! Hold metformin, IVF 500cc-1L D5NS prior to scan

CASE CONTINUED

1. CT Urogram

2. MR Urogram – If allergic to IV contrast

3. MR & Retrograde Pyelograms – If poor renal function

What about Renal Ultrasound? Not sensitive – 50% sensitive Not specific – 95% specific (RCC) Technician/body habitus dependent Not sufficient

AMH – ALTERNATIVE IMAGING

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012El-Galley R, Abo-Kamil R, Burns JR et al: Practical use of investigations in patients with hematuria. J Endourol 2008; 22: 51

If you refer microscopic hematuria frequently… Find urologist you trust. Ask them their preferences on imaging.

Modality Preferred imaging location?

Referrals to me? Don’t image please – let me discuss with patient I send prior imaging to my radiologists for comparison I show patients their imaging I give them a copy of their report If you do image, obtain study at RIMI & cc results to me. Care New England…in process of bringing reporting/image

viewing up to speed. CTU is preferred modality If ever any question text me or call my cell phone 585-315-4853

AMH –IMAGING SUMMARY

“Use of urine cytology and urine markers (NMP22, BTA-stat, & FISH) is NOT recommended” Cytology – Specific, Finds High Grade Tumors FISH/ Urovision (False Positive)

Chromosome 3,7, and 17 centromere gain. Loss of 9P21.

NMP 22 (False Positive) Detects nuclear matrix protein

BTA-Stat (False Positive) Detects compliment factor H-related protein

AMH – TUMOR MARKERS

Diagnosis, evaluation and follow-up of AMH in adults: AUA guideline, 2012Lotan, Y and Shariat, S.: Urinary Markers for Bladder Cancer Detection and Follow-up. AUA Update Series. Lesson 21 Volume 30, 2011

Any questions before I need to run?

THANK YOU

ASYMPTOMATIC MICROHEMATURIA VS. GROSS HEMATURIA

Initial supportive care: correct coag, consider transfusion, medical evaluation (in case OR requrired), stop all anticoagulation

Consider placing a Foley2 way minimum 20 Fr- hand irrigation3 way minimum 22 Fr

Must hand irrigate all clot free before starting CBI Start CBI with normal saline - titrate to light pink

GROSS HEMATURIA TREATMENT

Additional therapies

Amicar- IV, PO or intravesical

Must have no clot in bladder

Intravesical: Amicar, alum, formalin, silver nitrate.

Hyperbaric Oxygen

Cystoscopic evaluation with clot evacuation and fulguration.

GROSS HEMATURIA TREATMENT

The pregnant female AMH patient requires special consideration. The majority of AMH cases are associated with non-life threatening conditions, and less than 5% are associated with malignancy. Further, the incidence of AMH in pregnant and non-pregnant women is similar (approximately 4%).176 Brown177 reported that women with and without AMH during pregnancy had offspring of similar birth weight and gestational age at delivery, and similar rates of gestational hypertension and pre-eclampsia. Given that malignancies in this low risk group (typically < 40 years of age) are rare, the Panel recommends use of MRU, MRI with RPGs, or US to screen for major renal lesions with a full workup after delivery once gynecological bleeding and persistent infection have been ruled out.

SPECIAL CONSIDERATIONS IN THE PREGNANT FEMALE

The use of urine cytology and urine markers (NMP22, BTA-stat, and UroVysion FISH) is NOT recommended as a part of the routine evaluation of the asymptomatic microhematuria patient. Recommendation

Twenty-five studies reported sensitivity and/or specificity values for urine cytology.25-26, 32, 36, 42, 53, 59, 65, 178-194 Sensitivity values ranged from 0% to 100%; specificity values ranged from 62.5% to 100%.

For NMP22, sensitivities ranged from 6.0% to 100% and specificities ranged from 62% to 92%.

Three studies reported on UroVysion FISH;25, 191-192 sensitivities ranged from 61% to 100%, and specificities ranged from 71.4% to 93%.