hematuria, kidney & bladder cancer for the primary care physician shandra wilson, md june...
TRANSCRIPT
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Hematuria, Kidney & Bladder Cancer for the Primary Care
Physician Shandra Wilson, MD
June 4th,2013
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Overview
Hematuria – work-upCases
What’s new in bladder cancerWhat’s new in kidney cancer
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Definition of Microscopic Hematuria
3 or more RBC/hpf 3 specimens 3 weeks
AAFP.org, March 15, 2001
AUA Best Practice Guidelines, 2001
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Definition of Microscopic Hematuria
AAFP – “Best Practice” guidelines No major organization currently recommends
screening for microscopic hematuria in asymptomatic adults
USPTF – Grade “I” 2012 unclear of benefit of screening in asymptomatic
population
AAFP.org, March 15, 2001
AUA Best Practice Guidelines, 2001
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Prevalence of Microscopic Hematuria
0.18% - 18% of the population
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Long-term Follow-Up Micro Hematuria
1.2 million male and female adolescents Aged 16 to 25 years in Isreal Urine screening, 21 yrs of follow-up 0.3% had isolated micro hematuria ESRD 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 hematuria
Vivante, et al JAMA. 2011;306(7):764-765
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Dipstick Proteinuria and Mortality
Alberta Kidney Disease Network 920 000 individuals in Canada Dipstick proteinuria (Tr or 1+) 7.8% HR of 2.1 for all-cause mortality HR 2.7 doubling serum creatinine 1.7 for ESRD in pts with normal GFR Meta-analysis dipstick proteinuria of trace or
greater 8% overall increased risk all-cause mortality, even in pts 65 yrs or younger
Hemmelgarn BR, et al. JAMA. 2010;303(5):423-429
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Non-bloody red urine
Beets Blackberries Drugs (pyridium)
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Most Common Causes of Hematuria
UTI BPH Nephrolithiasis Idiopathic Genitourinary cancer
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Other Causes of Hematuria
Radiation cystitis Arteriovenous malformation Medical renal disease Trauma Exercise-induced hematuria Coagulopathy Benign familial/essential hematuria Papillary necrosis
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Odds of Finding Pathology
40-90% of gross hematuria 5-10% of microscopic hematuria
At least 40% of the time no etiology is found for asymptomatic microscopic hematuria
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History of Present Illness
Dysuria? Frequency? Recent respiratory infection? Menstruation? Previous episodes, work-up
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Past Medical History
h/o stones h/o XRT h/o bleeding disorders
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Medications
Pyridium Analgesic abuse
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Social History
Smoking Exposure to dyes, chemicals Exercise patterns
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Physical Exam
Age (cancer) Hypertension (associated with nephritis) Edema (associated with nephrotic syndrome) Pain – suprapubic, flank (infection) Possible DRE –(BPH)
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Laboratory Evaluation
UA, microscopy Urine culture Consider CBC Consider Creatinine
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3 Rules to Remember
Survey upper & lower tracts (cytology <35 reasonable instead of cysto)
Recheck urine after tx for UTI or stone If patient has any of the following – refer to
nephrology Dysmorphic RBC’s RBC casts, acanthotosis Proteinuria >500mg/dl
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Ideal Upper Tract Study
CT Urogram 3 phases Non-contrast to r/o calculi Nephrogenic phase to evaluate parenchyma Excretion phase to evaluate GU lining
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Lower Tract Evaluation
Depends on age and risk factors Cystoscopy (CT misses CIS which is flat)
Not necessary for non-smokers under 35yo Cytology on all patients
BTA stat; NMP22; UroVysion unclear positioning in algorithm right now
Cytology has accuracy issues too FISH more expensive, objective
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No Sx of Primary Renal Dz, AUA
Age <35 Non-smoker
No chemical exposure
Upper tract imagingCytology
Positive Cytology:Cystoscopy
And treatment
Negative cytologyConsider BP, cytol 1 yr *
Age > 35
Cytology,Upper tract
ImagingCystoscopy
Positive: TreatNegative:
Consider BP, cytol1 yr *
Persistent hematuriaHTN, protenuriaEval for renal dz
Gross hematuriaAbnl cytol
Irratative sx:Repeat complete eval
* With complete work-up, the risk of missing malignancy is <1%
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Case Studies
42 yo mother of one-year-old twins complains of gross hematuria
How do you proceed?
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History and Physical Exam
No dysuria/frequency/pain No h/o respiratory infection or stones No history of coagulopathy/non menstrual No history of radiation or surgery x c/s Non-smoker no chemical exposure
Now what?
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Laboratory Evaluation
UA shows RBC’s CBC normal Creatinine normal No UTI on culture
Now what?
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No Sx of Primary Renal Dz
Age <40 Non-smoker
No chemical exposure
Upper tract imagingCytology
Positive Cytology:Cystoscopy
And treatment
Negative cytologyConsider BP, cytol 1 yr *
Age > 40
Cytology,Upper tract
ImagingCystoscopy
Positive: TreatNegative:
Consider BP, cytol1 yr *
Persistent hematuriaHTN, protenuriaEval for renal dz
Gross hematuriaAbnl cytol
Irratative sx:Repeat complete eval
* With complete work-up, the risk of missing malignancy is <1%
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Upper and Lower Tract Imaging
US showed no abnormality of the kidneys Bladder US was unclear
Now what?
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Logical Algorithm
Cytologies should be performed. Her cytology would have been abnormal and cystoscopy, biopsy would have been done showing bladder cancer.
What happened: Took patient to the operating room for abdominal
exploration; husband called me on POD#1 to transfer Entered bladder and spilled tumor throughout
abdomen increasing risk of death dramatically Patient required chemotherapy and cystectomy for
spilled bladder cancer I am working with patient’s attorneys to find possible
reasonable settlement
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Case 2
59 yo volunteer at Colorado Springs Zoo Gross hematuria with flank pain
Now what?
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History and Physical
No dysuria/frequency/pain No h/o respiratory infection No history of coagulopathy No history of radiation or surgery Non-smoker no chemical exposure
Now what?
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Laboratory Evaluation
UA shows RBC’s CBC normal Creatinine normal No UTI on culture PSA done 3 months ago: 2.3ng/dl
Now what?
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Upper and Lower Tract Imaging
CT scan abd shows L kidney stone 1x1cm Cytologies are atypical
Now what?
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Rules to Remember
Survey upper and lower tracts Recheck urine after tx for UTI or stone If patient has any of the following – refer
to nephrology for a glomerular problem Dysmorphic RBC’s RBC casts Proteinuria >500mg/dl
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What Happened
Pt had his kidney stone treated with shock-wave lithotripsy
Meanwhile a bladder tumor grew in his bladder for a year
Finally he underwent cystoscopy, biopsy, and eventually cystectomy
I have worked with his attorneys to figure out if compensation is reasonable
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Case 3
23 yo female with malaise goes to ED with microscopic hematuria
Work up?
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History and Physical
Some dysuria/frequency/pain Generally feels crummy Possibly pregnant per her report No history of coagulopathy No history of radiation or surgery No chemical exposure Has smoked since she was 14yo
Now what?
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Lab Evaluation
UA shows protein, RBC’s & Bacteria HCT 39% Creatinine 1.1 < 100,000 colonies strep on culture bHCG negative
Now what?
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Upper and Lower Tract Evaluation
Renal/bladder US – no obvious tumor Cytologies – negative
Does she need anything else?
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No Sx of Primary Renal Dz
Age <40 Non-smoker
No chemical exposure
Upper tract imagingCytology
Positive Cytology:Cystoscopy
And treatment
Negative cytologyConsider BP, cytol 1 yr *
Age > 40
Cytology,Upper tract
ImagingCystoscopy
Positive: TreatNegative:
Consider BP, cytol1 yr *
Persistent hematuriaHTN, protenuriaEval for renal dz
Gross hematuriaAbnl cytol
Irratative sx:Repeat complete eval
* With complete work-up, the risk of missing malignancy is <1%
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What Happened
Pt sent home with antibiotics for UTI Pt advised to f/u with gynecology Pt returned to the ED 2 more times over 6
months Ultimately diagnosed with glomerular disease
requiring intensive medical therapy Pt sought legal advice for delay in diagnosis
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Hematuria Summary
Algorithm for hematuria is straight-forward and makes sense
Follow the algorithm for hematuria when presented with a patient
Do not screen for microscopic hematuria Remember the stats:
90% of pts with gross hematuria have pathology 90% of pts with microscopic hematuria do not
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Bladder cancer
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Colorado 18.7% 2007
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Pioglitazone (Actos) & Bladder Ca
115,727 new users of oral hypoglycemic agents
470 patients diagnosed with bladder cancer 6,699 controls Increased risk of bladder cancer (1.83 hazard rate)
Highest rate: patient exposed>24 mo’s (HR 1.99)
Cumulative dose > 28,000mg (HR 2.54)
Azoulay et al. BMJ 2012 344:e3645
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Life Time risk of Bladder Cancer
1.17% of men 50-70yo develop TCC 0.34% women 50-70yo develop TCC Overall risk for all: 2.4% in the U.S. 70%-85% do not require cystectomy
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How are we doing?
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Superficial Bladder Cancer
Greater 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-up A statistically significant survival advantage
was seen in patients who received at least half of the recommended care
Saigal, CK et al. Cancer 2012 118(5):1412-21
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Quick Review-Superficial/NMI
Superficial low grade disease: Strong survival (98%+), recurrence rates 30%
Non-muscle invasive, high grade disease: Up to 20% require cystectomy; recurrence 60%+ Multiple tumors Many recurrences Large tumors Progression in stage or grade BCG intravesically (mounts immune response)
Surveillance cystoscopy, maintenance treatments
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FGFR3 Mutation Related to Favorable T1 disease
132 patient with pT1 bladder cancer from 2 academic centers
FGFR mutations in 37% of cases FGFR 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
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Decrease in bladder cancer recurrence with Hexaminolevulinate enabled Fluorescence
551 participants, prospective study Randomization between white light & blue light
cystoscopy with Hex (5-aminolevulinic acid) Median time to recurrence 9.4 mo’s white Median time to recurrence 16.4 mo’s 5ALA/blue Cystectomy 7.9% white Cystectomy 4.8% 5ALA/blue (p=0.16)
$850 and 2 hours prep for 5-ALA wash 5-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
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Invasive Dz:National Cancer Database
40,388 patients with muscle invasive TCC Stage 2-4; Age 18-99 Patients treated with cystectomy: 42.9% Patients treated with radiation: 16.6% Both figures are stable between 2003-2007
Average survival without treatment: 15 mos.
U Fedili; J Urol 2011 185(1):72-8
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Review: Ileal Conduit Diversion
Advantages of Ileal Conduit Shorter operative time Quicker recovery Ease of care by others Less reabsorption of urine Preferred for radiation patients
Disadvantages Ileal Conduit External appliance Hernia at least 25% Skin irritation
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Continent Cutaneous Diversion
Advantages of continent cutaneous diversion Does not use urethra Minimal change in external body image No appliance required
Disadvantages of a continent cutaneous diversion Need for regular catheterization Risk for reoperation for complications Nitrogen absorption
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Orthotopic Continent Diversion
Advantages neobladder No need for external appliance High daytime continence rate (93%) Least change in lifestyle
Disadvantages of a neobladder Possible need for regular catheterization (5-20%) Nocturnal incontinence 10-30% Reabsorption of nitrogen
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………………………………………………………
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How much has gone on in your world in the last 10 years?
NCI website, 2010
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What are we doing differently?
Griffiths G. JCO 2011;29(16):2171-7
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National Trends, Cont.
% receiving chemotherapy: 27% 2003 34.5% 2007
Our data: 8.3% 2005 24.6% 2010
Now recommended by EORTC w level 1 evidence
U Fedili; J Urol 2011 185(1):72-8
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National Trends Cont.
Shifting medical climate to “outcomes” Complication 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
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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):777-83
Bladder 4% Colon 3%
Esophagus 17%Lung 6%
Pancreas 5% Stomach 6%
Survival and High v. Low Volume Hospitals
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ROBOTICS! Our world is changing!
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Now – Our New World
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Introduced in 2000 in Europe and US Laparoscopic surgery using a robotic
interface 5:1 and 10:1 magnification 3D visualization Normal surgical manipulation Finger tip instrument control Screen-in-screen technology Fluorescence technology Tremor reducing technology
Robotics History
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Robotics History
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Robotic cystectomy
Robotic Open p value
Mean EBL(ml) 258 575 <0.0001
OR time(hr) 4.20 3.52 <0.0001
Time to flatus(d) 2.3 3.2 0.0013
Time to BM(d) 3.2 4.3 0.0008
Analgesia(mg) 89.0 147 0.0044
Length of stay(d) 5.1 6.0 0.2387
Decreased QOL 2.3 2.6 0.5622Eur Urol 2010; 57(2):196
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Our Data
Estimated blood loss Robotic: 697 cc’s Open: 1202 cc’s
Transfusion rate: Robotic: 9% Open: 61%
Rate of re-operation identical at 1.4% (hernia, ureteral stricture, wound closure, abscess)
Death within 30 days of surgery: Robotic: 0% Open: 2.6%
Same distribution of diversions 27% ileal conduit 3% continent diversion to skin 70% orthotopic neobladder
University of Colorado 2003-2011
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How do you do this with a Robot?
http://youtu.be/Kq-_riKtzsY
http://www.youtube.com/watch?v=l8akuiW52ZI&feature=player_detailpage
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Robotics and Kidney Cancer
Evolution: Open nephrectomy
Removal of rib Opening in pleural cavity
Open partial nephrectomy Laparoscopic nephrectomy Laparoscopic partial nephrectomy Robotic partial nephrectomy (gold standard)
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New: Robotic Partial Nephrectomy
Laparoscopic v. Robotic Partial Nephrectomy
RPN LPN p value
Operative time (min) 140 156 0.04
Warm ischemic time 19 25 0.03
EBL (mL) 136 173 .05
Length of Stay (d) 2.5 2.9 .03
Tumor size (cm) 2.5 2.4 NS
Positive margin (n) 1 1 NS
Pelvicaliceal repair (%) 56 56 NS
Urology 2009 73(2):306-10
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Review of National Comprehensive Cancer Network (NCCN) Guidelines - Kidney Cancer
65,000 Americans will be diagnosed with renal cancer in 2012
20% (13,500) expected to die of disease RCC has increased by 2% annually for the
last 50 years - in part due to scanning Only 10% of patients have the triad of flank
pain, hematuria, and a flank mass Most renal tumors are now found incidentally
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UCLA Integrated Staging System
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UCLA Integrated Staging
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Renal Cell Cancer Review
It is recommended that patients with stage Ia undergo partial nephrectomy if possible (<4cm)
Partial nephrectomy is also recommended for stage Ib if technically feasible as well (4-7cm)
For stage II or greater a radical nephrectomy is usually required
Although distant recurrence-free survival rates are comparable, thermal ablation has been associated with an increased risk of local recurrence
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Renal Cell Cancer Review
Patient selection is important to identify those how might benefit from cytoreductive nephrectomy Good performance status Pulmonary mets Non-sarcomatoid pathology
Resection of a solitary metastasis has been shown to be associated with long-term survival in a subset of patients
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Renal Cell Cancer Review
Pazopanib approved in late 2009 VEGF, PDGF, and c-KIT receptor inhibitor PFS 11 months v. 2.8 months (placebo)
Sunitinib approved 2006 PDGFR, VEGF, c-KIT and CSF 31% 1-year PFS Sunitinib v. 6% for IFN-a
High Dose IL-2 still considered as a first line 4% remission significant toxicity
mTOR inhibitors and Sorafenib used in refractory cases No convincing data for adjuvant therapy
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Summary
Follow the algorithm for hematuria Send patients with renal or bladder
masses for surgical evaluation Call/email with questions or concerns
[email protected] 303-941-7168