Hematuria, Kidney & Bladder Cancer for the Primary Care Physician Shandra Wilson, MD

Hematuria, Kidney, Bladder Cancer for the Primary Care Physician

Hematuria, Kidney & Bladder Cancer for the Primary Care Physician Shandra Wilson, MD

June 4th,2013OverviewHematuria work-upCasesWhats new in bladder cancerWhats new in kidney cancer

2Definition of Microscopic Hematuria3 or more RBC/hpf3 specimens3 weeksAAFP.org, March 15, 2001AUA Best Practice Guidelines, 2001Definition of Microscopic HematuriaAAFP Best Practice guidelines No major organization currently recommends screening for microscopic hematuria in asymptomatic adults

USPTF Grade I 2012unclear of benefit of screening in asymptomatic population

AAFP.org, March 15, 2001AUA Best Practice Guidelines, 2001

Prevalence of Microscopic Hematuria0.18% - 18% of the population

Long-term Follow-Up Micro Hematuria1.2 million male and female adolescents Aged 16 to 25 years in IsrealUrine screening, 21 yrs of follow-up0.3% had isolated micro hematuriaESRD developed in 0.70% w/ micro hematuria, 0.045% w/o micro hematuria initially (HR =18.5; 95% CI 12.4-27.6)4.3% of all pts with ESRD had micro hematuriaVivante, et al JAMA. 2011;306(7):764-765

Title of article the time has come to recommend urine screening routinely6Dipstick Proteinuria and MortalityAlberta Kidney Disease Network920000 individuals in CanadaDipstick proteinuria (Tr or 1+) 7.8%HR of 2.1 for all-cause mortalityHR 2.7 doubling serum creatinine 1.7 for ESRD in pts with normal GFRMeta-analysis dipstick proteinuria of trace or greater 8% overall increased risk all-cause mortality, even in pts 65 yrs or youngerHemmelgarnBR, et al.JAMA.2010;303(5):423-429

Recommended if proteinuria positive albumin lever in urine tested

Clear evidence that starting an ACE inhibitor or Angiotensin 2 blocker early decreases ESRD here7Non-bloody red urineBeetsBlackberriesDrugs (pyridium)

Most Common Causes of HematuriaUTI BPH Nephrolithiasis Idiopathic Genitourinary cancer

Other Causes of HematuriaRadiation cystitisArteriovenous malformationMedical renal diseaseTraumaExercise-induced hematuriaCoagulopathyBenign familial/essential hematuriaPapillary necrosis

Odds of Finding Pathology40-90% of gross hematuria5-10% of microscopic hematuria

At least 40% of the time no etiology is found for asymptomatic microscopic hematuriaHistory of Present IllnessDysuria?Frequency?Recent respiratory infection?Menstruation?Previous episodes, work-upPast Medical Historyh/o stonesh/o XRTh/o bleeding disordersMedicationsPyridiumAnalgesic abuse

Social HistorySmokingExposure to dyes, chemicalsExercise patterns

Physical ExamAge (cancer)Hypertension (associated with nephritis)Edema (associated with nephrotic syndrome)Pain suprapubic, flank (infection)Possible DRE (BPH)

Laboratory EvaluationUA, microscopyUrine cultureConsider CBCConsider Creatinine

3 Rules to RememberSurvey upper & lower tracts (cytology 500mg/dl

Ideal Upper Tract StudyCT Urogram3 phasesNon-contrast to r/o calculiNephrogenic phase to evaluate parenchymaExcretion phase to evaluate GU lining

Lower Tract EvaluationDepends on age and risk factorsCystoscopy (CT misses CIS which is flat)Not necessary for non-smokers under 35yoCytology on all patientsBTA stat; NMP22; UroVysion unclear positioning in algorithm right nowCytology has accuracy issues tooFISH more expensive, objective

No Sx of Primary Renal Dz, AUA Age 35Cytology,Upper tract ImagingCystoscopyPositive: TreatNegative: Consider BP, cytol1 yr *Persistent hematuriaHTN, protenuriaEval for renal dzGross hematuriaAbnl cytolIrratative sx:Repeat complete eval* With complete work-up, the risk of missing malignancy is 28,000mg (HR 2.54)

Azoulay et al. BMJ 2012 344:e3645Life Time risk of Bladder Cancer1.17% of men 50-70yo develop TCC 0.34% women 50-70yo develop TCCOverall risk for all: 2.4% in the U.S.70%-85% do not require cystectomy

How are we doing?

Superficial Bladder CancerGreater than 98% of patients with bladder cancer have bleeding within 3 months of developing tumor (autopsy studies)Yet, recent SEER study evaluated 4,790 patients with NMI bladder cancer. Only 1 received appropriate treatment and follow-upA statistically significant survival advantage was seen in patients who received at least half of the recommended careSaigal, CK et al. Cancer 2012 118(5):1412-21

Quick Review-Superficial/NMISuperficial low grade disease: Strong survival (98%+), recurrence rates 30%Non-muscle invasive, high grade disease: Up to 20% require cystectomy; recurrence 60%+Multiple tumorsMany recurrencesLarge tumorsProgression in stage or gradeBCG intravesically (mounts immune response)Surveillance cystoscopy, maintenance treatments

FGFR3 Mutation Related to Favorable T1 disease132 patient with pT1 bladder cancer from 2 academic centersFGFR mutations in 37% of casesFGFR correlated with lower grade tumors Lack of FGFR mutation and CIS were significant for predicting progression in univariate analysis at 6.5 years (P =0.01)Van Rhijn J Urol 2012; 187(1):310

Decrease in bladder cancer recurrence with Hexaminolevulinate enabled Fluorescence551 participants, prospective studyRandomization between white light & blue light cystoscopy with Hex (5-aminolevulinic acid)Median time to recurrence 9.4 mos whiteMedian time to recurrence 16.4 mos 5ALA/blueCystectomy 7.9% whiteCystectomy 4.8% 5ALA/blue (p=0.16)$850 and 2 hours prep for 5-ALA wash5-ALA is a component of heme synthesis and is taken up by cancerous cells most effectively

Grossman HB; J Urol 2012 188(1):58-62http://www.youtube.com/watch?v=0aa-6WQLaPM

Invasive Dz:National Cancer Database40,388 patients with muscle invasive TCCStage 2-4; Age 18-99Patients treated with cystectomy: 42.9%Patients treated with radiation: 16.6%Both figures are stable between 2003-2007Average survival without treatment: 15 mos. U Fedili; J Urol 2011 185(1):72-8

Review: Ileal Conduit DiversionAdvantages of Ileal ConduitShorter operative timeQuicker recoveryEase of care by othersLess reabsorption of urinePreferred for radiation patients

Disadvantages Ileal ConduitExternal applianceHernia at least 25%Skin irritation

Continent Cutaneous DiversionAdvantages of continent cutaneous diversionDoes not use urethraMinimal change in external body imageNo appliance requiredDisadvantages of a continent cutaneous diversionNeed for regular catheterizationRisk for reoperation for complicationsNitrogen absorption

Orthotopic Continent DiversionAdvantages neobladderNo need for external applianceHigh daytime continence rate (93%)Least change in lifestyle

Disadvantages of a neobladderPossible need for regular catheterization (5-20%)Nocturnal incontinence 10-30%Reabsorption of nitrogen

How much has gone on in your world in the last 10 years?NCI website, 201056What are we doing differently? Griffiths G. JCO 2011;29(16):2171-7

57This article presents the long-term results of the international multicenter randomized trial that investigated the use of neoadjuvant cisplatin, methotrexate, and vinblastine (CMV) chemotherapy in patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy. Nine hundred seventy-six patients were recruited between 1989 and 1995, and median follow-up is now 8.0 years. National Trends, Cont.% receiving chemotherapy: 27% 2003 34.5% 2007Our data: 8.3% 2005 24.6% 2010Now recommended by EORTC w level 1 evidence

U Fedili; J Urol 2011 185(1):72-8National Trends Cont.Shifting medical climate to outcomesComplication rates of cystectomy becoming more defined and range from 40-80%Peri-operative mortality rate 2.6%Mortality higher at low volume hospitals (OR 1.7)Eur Urol 57(2): Feb 2010, 274-282

KM plots describing 5-year survival among patients undergoing cancer resection at low-, medium-, and high-volume hospitals, based on data from the SEER-Medicare linked database, 1992-2002; JD Birkmeyer, Annals of Surg 2007. 245(5):777-83Bladder 4%Colon 3%Esophagus 17%Lung 6%Pancreas 5%Stomach 6%Survival and High v. Low Volume HospitalsROBOTICS! Our world is changing!

Now Our New World

oooo Introduced in 2000 in Europe and USLaparoscopic surgery using a robotic interface5:1 and 10:1 magnification 3D visualizationNormal surgical manipulationFinger tip instrument controlScreen-in-screen technologyFluorescence technologyTremor reducing technology

Robotics History

Robotics History

Robotic cystectomyRobotic Open p value Mean EBL(ml) 258 575